Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.85919982 |
On the basis of immunofluorescence studies , a model has been proposed that when c Src is activated , it is redistributed to podosomes , in which substrates become phosphorylated , creating binding sites for CSK . 0.85919982^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.54459375 |
To test a nonreceptor tyrosine kinase , we then expressed the human proto oncogene c src together with its negative regulator Csk . 0.54459375^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.6900855 |
Although we have shown that the Csk Src homology 2 domain can bind to several tyrosine phosphorylated proteins , including pp125FAK and paxillin , a majority of protein which bound to Csk was IRS 1 when cells were stimulated by insulin . 0.6900855^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.62051185 |
An association between CSK and c Src was detected by immunoprecipitation following IGF 1 stimulation of differentiating but not proliferating 3T3 L 1 cells . 0.62051185^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
At the enzyme level , we observed that c Src kinase preferentially phosphorylates alpha casein , while the 5 Src kinase prefers beta casein . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Platelet activation leads to increased c src kinase activity and association of c src with an 85 kDa tyrosine phosphoprotein . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Inhibition of the autocrine angiotensin system with the converting enzyme inhibitor or the receptor antagonist also leads to increased expression of the proto oncogene c src : pp60c src mRNA increased 7 11 fold , c src protein 3 fold , and c src kinase activity 2 3 fold . ^^^ Constitutively increased c src kinase activity reconstituted the increases in migration and u PA observed with angiotensin system interruption . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Our human clone is 98 % identical at the aa level to a gene which was isolated independently from neonatal rat brain and was termed csk for c src kinase . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Since complex formation between c Src and CSK seemed a likely regulatory step in the control of c Src kinase activity , such an association was investigated by immunoprecipitation and Western blotting as well as intracellular localization studies . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Phosphorylation of pp60c src by p34cdc2 at three amino proximal serine / threonine residues is temporally correlated with , but insufficient for , mitotic activation of c Src kinase . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Activation of c Src kinase was accompanied by tyrosine dephosphorylation , which might be explained by a rapid increase in intracellular protein tyrosine phosphatase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To investigate how c Src kinase activity is regulated in vivo , we first looked at whether 5 Crk can activate c Src kinase . ^^^ We found that cooverexpression of 5 Crk and c Src caused elevation of c Src kinase activity , resulting in an increase of tyrosine phosphorylation of cellular proteins and morphological transformation of rat 3Y1 fibroblasts . 5 Crk and c Src complexes were not detected , although 5 Crk bound to a variety of tyrosine phosphorylated proteins in cells overexpressing 5 Crk and c Src . ^^^ Overexpression of Csk in these transformed cells caused reversion to normal phenotypes and also reduced the level of c Src kinase activity . ^^^ These results strongly suggest that Csk acts on Tyr 527 of c Src and suppresses c Src kinase activity in vivo . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Segments of regenerated nerve , extracted at various times following nerve transection , showed an induction of in vitro c src kinase activity as measured by autophosphorylation of immunoprecipitated pp60c src . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Triton 10 100 extracts of plasma membranes of bovine brain contain a heat stable factor that stimulates c src kinase activity with any of the polymers as substrate . ^^^ The same extract contains a heat labile factor that preferentially inhibits c src kinase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The protein GST TK 7 was phosphorylated by c src with a KM of 5 10 microM , which indicated a potential interaction between the connecting segment of the EGFR and the c src kinase . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The epidermal growth factor ( EGF ) receptor kinase and c src kinase were inhibited in vitro with IC 50 values in the range of 1 7 microM . ^^^ Thus , in these cell lines , members of the c src kinase family are also potential targets for inhibition by the compounds . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Immune complex kinase assays of K 562 cells with an anti src serum ( GD 11 ) yielded active c src kinase and a Mr 50 , 000 phosphorylated protein , both of which were resistant to alkaline hydrolysis . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In an immune complex protein kinase assay , all seven cell lines displayed c src kinase activity which was considerably higher than that found in nonneurocrine cells ( human diploid fibroblasts , glioma , and non small cell lung carcinoma cell lines ) . ^^^ Furthermore , the c src kinase activity , as determined by autophosphorylation or phosphorylation of an exogenous substrate , enolase , correlated with the stage of neurocrine differentiation . ^^^ There was an approximately 30 fold difference in c src kinase autophosphorylation activity between the cell lines representing the highest and lowest stages of neurocrine differentiation . ^^^ In summary , we found a clear correlation between c src kinase activity and the stage of neuronal and neuroendocrine differentiation . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Fertilization results in a decrease in the c src kinase detectable by this technique suggesting that c src does not contribute to the fertilization induced increase in protein tyrosine kinase activity . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk ( C terminal Src kinase ) , a protein tyrosine kinase , bearing the Src homology 2 and 3 ( SH 2 and SH 3 ) domains , has been implicated in phosphorylation of c Src Tyr 527 , resulting in suppression of c Src kinase activity . ^^^ The activity of the c Src kinase localized at the focal adhesion plaques appears to be regulated by cell adhesion to the extracellular matrix . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Regulation of c Fgr protein kinase by c Src kinase ( CSK ) and by polycationic effectors . ^^^ The protein tyrosine kinase expressed by the protooncogene c fgr is phosphorylated and down regulated in vitro by the c Src kinase ( CSK ) . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Functional interaction between the epidermal growth factor receptor and c Src kinase activity . ^^^ However , the cell line over expressing the EGF R showed a twofold enhancement of c Src kinase activity after EGF stimulation . ^^^ The activation of c Src kinase by EGF was confirmed in other EGF R expressing cell types . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition , it has been shown previously that occupancy of the c Src SH 2 domain with a phosphopeptide stimulates c Src kinase catalytic activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition , an increase in specific c Src kinase activity was observed in the cytoskeleton as well as in the cytosol and the membrane fraction . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
On the basis of indirect evidence , we previously suggested that this is caused by partial dephosphorylation at Tyr 527 , the phosphorylation of which suppresses c Src kinase activity . ^^^ Also , we show that an amino terminal mutation that prevents myristylation ( and membrane localization ) of c Src does not interfere with the p34cdc2 mediated phosphorylations but blocks both mitotic dephosphorylation of Tyr 527 ( in kinase defective Src ) and stimulation of c Src kinase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Previously we demonstrated that C3H10T1 / 2 murine fibroblasts overexpressing avian c src exhibit elevated levels of cyclic AMP ( cAMP ) in response to beta adrenergic agonists compared with that in control cells and that this enhanced response requires c src kinase activity ( W . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Signal transduction through extracellular signal regulated kinase like pp 57 blocked in differentiated colon carcinoma cells having low levels of c src kinase . ^^^ The decrease in tyrosine kinase activity was not due to down regulation of FGF receptors or their tyrosine kinase activities . c src kinase specific activity was decreased 4 5 fold in both goblet cell lines , suggesting a role for c src in pp 57 mediated signal transduction . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Since SH 2 domains recognize phosphotyrosine , it is possible that these two non catalytic domains associate , and thereby repress c Src kinase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This truncated c src expression system provides a good source of enzyme for diverse experiments and is an ideal model for understanding the implication of structural alterations in the catalytic activity of the c src kinase by site directed mutagenesis experiments . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Malignant osteopetrosis : c src kinase is not reduced in fibroblasts . ^^^ No differences could be detected in c src protein and c src kinase activity levels between fibroblasts from healthy controls and affected individuals . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Current models predict that inhibition of c Src kinase activity results from an interaction of phosphorylated Tyr 527 with the amino terminal SH 2 domain . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The broad band of semi purified p 130 became sharp at an elevated position in the gel upon treatment with orthovanadate in vivo or with c Src kinase produced using a baculovirus vector in vitro , whereas it shifted at a lower position upon treatment with alkaline phosphatase in vitro . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Neu induced mammary tumors possessed six to eightfold higher c Src kinase activity than the adjacent epithelium . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Low stringency screening of a complementary DNA library prepared from the human colon cancer derived cell line HT 29 with a probe containing the tyrosine kinase domain of human c src kinase led to the identification and isolation of a clone containing a receptor class tyrosine kinase . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The deduced amino acid sequence of the protein encoded by this gene was most homologous to CSK ( c src kinase ) . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Prolactin receptor is associated with c src kinase in rat liver . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
An increase in intracellular calcium levels is an early step in signal transduction by PDGF and serotonin in mesangial cells . c src kinase overexpression reduced PDGF and serotonin mediated changes in Ca2+ signaling , indicating multiple targets of pp60c src action . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Phosphorylation and dephosphorylation of Tyr 530 in human c Src ( Tyr 527 in avian c Src ) is critical in regulating c Src kinase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Epidermal growth factor receptor kinase , c src kinase , and focal adhesion kinase were phosphorylated on tyrosine with 32PO4 and incorporated into gels prior to electrophoresis . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
These data suggest that Gbetagamma subunit mediated formation of Shc . c Src complexes and c Src kinase activation are early events in Ras dependent activation of MAP kinase via pertussis toxin sensitive G protein coupled receptors . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The c src phosphorylation was associated with an inhibition of c src kinase activity , suggesting phosphorylation of tyrosine 527 in the c src regulatory domain . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Analysis of the gradients showed that the focal adhesion kinase was not associated with the integrin receptors under these experimental conditions , while about 26 % of the c Src kinase codistributed with the integrin receptor complex , and showed a molecular size and a distribution similar to that of a 59 kDa phosphoprotein comigrating with the alpha 6 beta 1 receptor . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Little is known about the regulatory mechanism of c Src kinase in cells except the suggested regulation through phosphorylation and dephosphorylation of its carboxyl terminal tyrosine residue ( Y 527 ) . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Consistent with these results , TCDD induced c Src kinase activity was abolished when c Src immunoprecipitate ' s suspension was preincubated with 0 . 1 or 1 microM alpha naphthoflavone ( AhR blocker ) for 10 min prior to the addition of TCDD . ^^^ In addition , pretreatment of 3T3 fibroblast cells with 3 methylcholanthrene abolished TCDD induced c Src kinase activity in AhR immunoprecipitate . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Caffeine pretreatment also inhibits hypoxia mediated c Src kinase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The c Src kinase activity was increased 2 . 9 fold following CSF 1 treatment . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Targeted manipulation of the c src kinase may be useful in modulating MC behavior in vivo . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We found that catalytic activity of the immunoprecipitated c Src kinase from NIH3T3 cells was elevated several folds by exposure to 0 . 5 50 microM of sulfhydryl reactive Hg2+ . ^^^ Further study revealed that Hg2+ was capable of activating the 5 Src kinase lacking Y 527 and the c Src kinase from mutant cells defective of the Y 527 phosphorylating Csk kinase . ^^^ Not like bivalent Hg2+ , monovalent p chloromercuribenzenesulfonic acid was incapable of activating c Src kinase . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This increased motility was accompanied by an EGF induced increase in c Src kinase activity , relocalisation of c Src to the cell periphery and phosphorylation of FAK in the carcinoma cells but not in the adenoma cells . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Further analyses revealed that c src kinase activity was dramatically elevated in cultured mouse keratinocytes exposed to EGF . ^^^ Concomittantly , erbB 2 : EGFr heterodimer formation and c src kinase activity were also elevated in TPA treated epidermis . ^^^ Activation of erbB 2 and c src kinase were also observed in the epidermis of TGF alpha transgenic mice where expression of human TGF alpha was targeted to basal keratinocytes with the human K 14 promoter . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Furthermore , Tyr 402 , which mediates the binding of RAFTK to c Src kinase , was required for the phosphorylation of the C terminal domain of p 130 ( Cas ) . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CONCLUSIONS : Cell density contributes to the regulation of c src kinase activity and VEGF expression in HT 29 cells . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Our findings are consistent with a specific regulation of mitogenesis by LMW PTP through a pathway involving c Src kinase but independent by both PI3K and ERK . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Alternatively , mRNA and protein levels of c src kinase ( CSK ) , which inactivates pp60c src by phosphorylating Y 527 , are not altered by the steroid . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The ITAMs of the A 74 protein are tyrosine phosphorylated by a c Src kinase in vitro . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Agonists of the CaR can stimulate increased c SRC kinase activity and increased extracellular signal regulated kinase 1 / mitogen activated protein kinase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The alpha1C subunit of the L type Ca2+ channel co immunoprecipitated with anti c Src and anti phosphotyrosine antibodies , indicating direct association of c Src kinase with the Ca2+ channel . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Similar results were obtained by analysis of c Src protein levels and c Src kinase activity as measured by Western blot and in vitro kinase assays of representative cases . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
One potential mechanism of action in colorectal cancer is the inhibition of c Src kinase activity , since this proto oncogene is hyperexpressed in human large bowel tumours . ^^^ Our results show that despite the 9 fold higher level of c Src kinase activity found in HT 29 cells , there was only a 1 . 4 fold difference in cytotoxicity as compared with BE cells , the latter being the most sensitive . ^^^ Moreover , even at concentrations of geldanamycin that resulted in cell kill of 80 % or more after a 24 h period of exposure , there was no effect on c Src kinase activity in HT 29 cells , although c Src protein was depleted at supralethal levels of exposure . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The contractile actions of both TF and EGF were accompanied by increases in tissue phosphotyrosyl proteins and an increase in tissue c src kinase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Our results show that interaction of IL 3 with its receptor leads to the activation of c Src kinase activity , which in turn facilitates the binding of c Src to STAT 3 . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
PD 158780 potently inhibited the LPA stimulated MAP kinase kinase 1 / 2 ( MKK1 / 2 ) activation and EGF receptor tyrosine phosphorylation in HeLa cells , while it had no detectable effect on c Src kinase activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
After treatment with TCDD , the activities of cytosolic AhR associated c Src kinase , microsomal protein kinase C ( nPKC epsilon ) , microsomal c Src kinase , nuclear p44 / 42 MAPK , c Jun N terminus kinase , and the amount of microsomal pan Ras protein were different in males and females . ^^^ TCDD did not decrease body or adipose tissue weights in transgenic src deficient male mice as compared to their wild type littermates , and the activity of AhR associated c Src kinase was not increased by TCDD in src deficient male mice . ^^^ The gender specific mechanisms of TCDD induced toxicity appear to involve c Src kinase , nPKC epsilon , and pan Ras , as well as overlap in the cytosolic signal transduction pathways of TCDD and sex steroids . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Epidermal growth factor receptor ( EGFR ) in whole testis was measured , as were the activities of c Src kinase , protein tyrosine kinase ( PTK ) , mitogen activated protein 2 kinase ( MAP2K also termed as Erk 2 ) , protein kinase A ( PKA ) , and protein kinase C ( PKC ) . ^^^ Although TCDD significantly increased c Src kinase activity in immature and mature rats , opposite effects of TCDD on activities of PTK , PKA , and PKC were found in 34 day old rats vs 49 , 62 , and 90 day old rats . ^^^ When 10 micrograms TCDD / kg was administered to 21 day old rat , 24 h after c Src kinase inhibitor geldanamycin , there was no testicular atrophy and no change in the daily sperm production was found . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Use of c Src and c Fos knockout mice for the studies on the role of c Src kinase signaling in the expression of toxicity of TCDD . ^^^ First , we could show that chemical inhibition of c src kinase could produce practically the same phenomenon of reduced toxicity of TCDD in wild type mice cotreated with geldanamycin , a specific chemical inhibitor known to suppress c src kinase . ^^^ Second , we established that the level of the Ah receptor associated with c src kinase ( 2 ) is indeed low in c src deficient mice as well as geldanamycin treated mice . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
A marked increase in the protein amount of H Ras and a significant increase in the activity of c Src kinase , PTK , and Erk 2 were found in cells from TCDD treated animals . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Activation of c src appeared to be dependent on active ErbB 2 tyrosine kinase , as the ErbB 2 inhibitor tyrphostin AG 825 blocked the induction of c src kinase activity , as well as the ability of transformed cells to grow on soft agar , but not plastic . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Specifically , the autophosphorylation site of FAK , which is a reported site of c Src kinase binding , is required for bacterial internalization , as overexpression of a derivative lacking the autophosphorylation site had a dominant interfering effect as well . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The reduced level of c Src kinase activity correlated with the levels of both PDGF receptor and DNA synthesis . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Studies of the mechanism of c Src regulation have suggested that c Src kinase activity is downregulated by phosphorylation of a critical carboxy terminal tyrosine ( Tyr 530 in human c Src , equivalent to Tyr 527 in chicken Src ) and have implied the existence of activating mutations in this C terminal regulatory region . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
These experiments demonstrate that activated Ret is able to bind and stimulate c Src kinase and that Src activation is essential for the mitogenic activity of Ret . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In conclusion , c Src plays a critical role in agonist stimulated cytoskeletal reorganization and signal transduction at focal adhesions in VSMCs . c Src kinase activity is required for the cytoskeletal turnover that occurs in cell spreading , whereas c Src appears to regulate actin bundling via a kinase independent mechanism . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Activation of c Src kinase is associated with in vitro decidualization of human endometrial stromal cells . ^^^ Withdrawal of both estrogen and progesterone from the cultures of decidualized stromal cells reduced c Src kinase activity to the basal level and also changed the pattern of tyrosine phosphorylation of the several cellular proteins to the unstimulated state . ^^^ Our findings suggest that the activation of c Src kinase may be a normal physiological event associated with decidualization , being specifically involved in the signaling cascades mediated by ovarian hormone stimulation . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Nitric oxide controls src kinase activity through a sulfhydryl group modification mediated Tyr 527 independent and Tyr 416 linked mechanism . c Src kinase was activated when either murine NIH3T3 fibroblast cells or immunoprecipitated c Src proteins were treated with nitric oxide generator , S nitroso N acetyl penicillamine ( SNAP ) or sodium nitroprusside . ^^^ Nitric oxide ( NO ) scavenger hemoglobin and N ( 2 ) O ( 3 ) scavenger homocysteine abolished the SNAP mediated c Src kinase activation . ^^^ Peptide mapping of in vivo labeled c Src kinase excluded the involvement of phospho Tyr 527 dephosphorylation in the SNAP mediated activation mechanism . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Sam 68 is a 68 kDa protein that associates with and is phosphorylated by the c Src kinase at mitosis . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To explore whether c Src kinase is involved in HGF induced cell growth , a mouse mammary carcinoma cell line ( SP 1 ) that co expresses HGF and Met and a nonmalignant epithelial cell line ( Mv1Lu ) that expresses Met but not HGF were used . ^^^ In this study , we have shown that c Src kinase activity is constitutively elevated in SP 1 cells and is induced in response to HGF in Mv1Lu cells . ^^^ In addition , c Src kinase associates with Met following stimulation with HGF . ^^^ The enhanced activity of c Src kinase also correlates with its ability to associate with Met . ^^^ Expression of a dominant negative double mutant of c Src ( SRC RF ) , lacking both kinase activity ( K295R ) and a regulatory tyrosine residue ( Y527F ) , in SP 1 cells significantly reduced c Src kinase activity and strongly blocked HGF induced motility and colony growth in soft agar . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In the present work , we studied the mechanisms underlying c Src kinase activation by PRL and the role that Jak 2 plays in this process . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
VEGF stimulation specifically activated c Src kinase activity but not that of other related Src kinases such as Lyn , Fyn , or Hck in KS cells . ^^^ Further studies using mutants of c Src kinase revealed that Src mediates mitogen activated protein kinase activation induced by VEGF . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The recombinant adenovirus vector carrying csk cDNA induced Csk expression in mouse osteoclast like cells formed in vitro and clearly reduced c Src kinase activity in a dose dependent manner . ^^^ Conversely , kinase inactive Csk caused an increase in c Src kinase activity and bone resorbing activity of the cells both in vitro and in vivo , acting as a dominant negative molecule against intrinsic Csk . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The receptor protein tyrosine phosphatase alpha ( PTPalpha ) is involved in the activation of c Src kinase as well as in down regulation of the insulin signal . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
They also show that c Src kinase activity can be used differently by individual extracellular stimuli , possibly contributing to their ability to generate unique cellular responses . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Furthermore AG 1478 , a specific inhibitor of the EGF receptor kinase , blocked Erk 1 and Erk 2 activation . c Src kinase was not involved in the IL 8 mediated phosphorylation of the EGF receptor , but was critical for Shc phosphorylation and downstream Erk1 / 2 kinase activation . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Here we show that feline cardiomyocyte lysate contains thermostable components that inhibit c Src kinase in vitro . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Using this model , we previously reported specific changes in the c Src kinase activity and tyrosine phosphorylation of several proteins during in vitro decidualization . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
However , c Src kinase or MEK1 / 2 activities are not required for the cell survival effect . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Integrin induced epidermal growth factor receptor ( EGFR ) phosphorylation also depended on both EGFR and c Src kinase activities . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Nanomolar amounts of alpha tocotrienol , but not alpha tocopherol , blocked glutamate induced death by suppressing glutamate induced early activation of c Src kinase . ^^^ Tocotrienol treatment prevented death of Src overexpressing cells treated with glutamate . alpha Tocotrienol did not influence activity of recombinant c Src kinase suggesting that its mechanism of action may include regulation of SH domains . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In c Src kinase reactions , polarization decreased with time as reaction products displaced the fluorescein labeled phosphopeptide from the anti phosphotyrosine antibodies . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Peroxynitrite treatment of human pancreatic carcinoma cells in vitro resulted in increased tyrosine nitration and tyrosine phosphorylation of c Src kinase , increased ( > 2 fold ) c Src kinase activity , and increased association between c Src kinase and its downstream substrate cortactin . ^^^ Collectively , these observations suggest that peroxynitrite mediated tyrosine nitration and tyrosine phosphorylation of c Src kinase may lead to enhanced tyrosine kinase signaling observed during pancreatic ductal adenocarcinoma growth and metastasis . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To explore the cellular mechanism whereby TNF alpha regulates phosphorylation of FAK in the liver , we measured c Src kinase activity and the abundance of 3 major protein tyrosine phosphatases ( PTPs ) ( PTP 1B , leukocyte antigen related tyrosine phosphatase [ LAR ] , and src homology 2 domain containing protein tyrosine phosphatase [ SHPTP 2 ] ) in liver homogenates from obese Zucker rats after TNF alpha blockade . ^^^ Hepatic c Src kinase activity was unaltered , but LAR protein was reduced by 75 % . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Recently , a subset of colon cancers have shown a nonsense mutation at codon 531 , which truncates c SRC directly C terminal to the c SRC kinase regulatory domain . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Biochemical and cellular effects of c Src kinase selective pyrido [ 2 , 3 d ] pyrimidine tyrosine kinase inhibitors . ^^^ The compounds were ATP competitive inhibitors of c Src kinase with IC ( 50 ) values < 10 nM and from 6 to > 100 fold selectivity for c Src tyrosine kinase relative to basic fibroblast growth factor receptor ( bFGFr ) tyrosine kinase , platelet derived growth factor receptor ( PDGFr ) tyrosine kinase , and epidermal growth factor receptor ( EGFr ) tyrosine kinase . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Our results show for the first time that Rap 1 mediates c Src kinase signaling and reveal mechanistic differences in the signaling properties of wild type and transforming Src proteins . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In vivo overexpression of PTP1B in 293 cells caused a 2 fold increase of endogenous c Src kinase activity . ^^^ Our findings indicate that PTP1B is the primary protein tyrosine phosphatase capable of dephosphorylating c Src in several human breast cancer cell lines and suggests a regulatory role for PTP1B in the control of c Src kinase activity . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
PP 1 at this concentration is known to inhibit c Fyn kinase , but not c Src kinase , and none of the three known Src family kinases ( c Src , c Fyn , and c Yes ) expressed in fibroblasts is activated by 5 Ha Ras . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Tyrosine 14 is now thought to be the principal site for recognition by c Src kinase ; however , little is known about this phosphorylation event . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In contrast to other cell types , IkappaBalpha , in bone marrow macrophages ( BMMs ) , which are osteoclast precursors , is tyrosine phosphorylated by c Src kinase . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Most importantly , interaction of extracellular matrix components ( e . g . , HA ) with cells triggers the cytoplasmic domain of CD 44 isoforms to bind its unique downstream effectors ( e . g . , the cytoskeletal protein ankyrin or various oncogenic signaling molecules Tiam 1 , RhoA activated ROK , c Src kinase and p185HER2 ) and to coordinate intracellular signaling pathways ( e . g . , Rho / Ras signaling and receptor linked / non receptor linked tyrosine kinase pathways ) , leading to a concomitant onset of multiple cellular functions ( e . g . , tumor cell growth , migration and invasion ) and breast tumor progression . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Furthermore , c Src kinase activity was found to be increased in the hypoxic condition , and in the presence of antisense of Src , there was down regulation of the total mRNA level and also the promoter activity of VPF / VEGF . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Adherent KYN 2 cells having a high level of c Src kinase activity become scattered , extend lamellipodia , and exhibit high motility . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The c Src kinase inhibitor PP 1 abrogated the actions of DETA / NO on cGMP formation , PKG activation , caspase activation , cytochrome c release from mitochondria , and Bcl 2 phosphorylation and degradation in serum deprived cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
It has been recently shown that the fast non genomic responses of 1 , 25 ( OH ) ( 2 ) vitamin D ( 3 ) [ 1 , 25 ( OH ) ( 2 ) D ( 3 ) ] in skeletal muscle cells involve tyrosine phosphorylation of MAP kinase ( ERK1 / 2 ) , c Src kinase and the oncoprotein c myc . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Taken together , these results demonstrate that 1 , 25 ( OH ) 2D3 stimulates proliferation associated signalling pathways in skeletal muscle cells and implicate c Src kinase as mediator of this response . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We show that in the early phases of cell adhesion integrins associate with EGF receptors on the cell membrane in a macromolecular complex including the adaptor protein p130Cas and the c Src kinase , the latter being required for adhesion dependent assembly of the macromolecular complex . ^^^ We also show that the integrin cytoplasmic tail , c Src kinase , and the p130Cas adaptor protein are required for phosphorylation of EGF receptor in response to integrin mediated adhesion . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The compounds are inactive or weakly active toward a number of other tyrosine kinases , including the FGF receptor 1 , EGF receptor , and c Src kinase , as well as toward serine threonine kinases , including different PKC isoforms and GRK 2 , and appear therefore selective for PDGF receptor inhibition . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The data support the hypothesis that activation of c src kinase plays a role in skin tumor promotion . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Transforming growth factor alpha prevents detachment induced inhibition of c Src kinase activity , Bcl XL down regulation , and apoptosis of intestinal epithelial cells . ^^^ TGF alpha exerts its anti anoikis effect by preventing detachment induced inhibition of c Src kinase activity . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We show that hnRNP K and the c Src kinase specifically interact with each other , leading to c Src activation and tyrosine phosphorylation of hnRNP K in vivo and in vitro . c Src mediated phosphorylation reversibly inhibits the binding of hnRNP K to the differentiation control element ( DICE ) of the LOX mRNA 3 ' untranslated region in vitro and specifically derepresses the translation of DICE bearing mRNAs in vivo . ^^^ Our results establish a novel role of c Src kinase in translational gene regulation and reveal a mechanism by which silenced mRNAs can be translationally activated . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Coupling of M 2 muscarinic receptor to L type Ca channel via c src kinase in rabbit colonic circular smooth muscle . ^^^ This study determined whether muscarinic receptor couples to Ca ( 2+ ) channels via c src kinase . ^^^ They also suggest a central role of c src kinase in the cross talk between tyrosine kinase receptor and GPCR . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In response to PTH , tyrosine phosphorylation of p85alpha was enhanced , effect that was abolished by PP 1 , the inhibitor of c Src kinase . ^^^ Taken together , the present study demonstrate , for the first time , that PTH rapidly and transiently stimulates PI3K activity and its down effector Akt / PKB in rat enterocytes playing c Src kinase a central role in PTH dependent PI3K activation and that PI3K signaling pathway contributes to PTH mediated MAPK activation . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Finally , overexpression of STAT 3 in Rat 2 cells transiently stimulated Hck and c Src kinase activity in the absence of extracellular signals , an effect that was dependent upon a putative SH 3 binding motif in STAT 3 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Changing all of these sites to phenylalanine resulted in a villin mutant that neither was phosphorylated in TKX 1 cells nor was a substrate for c src kinase in an in vitro kinase assay . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We have now examined whether c Src kinase is similarly phosphorylated and activated in response to the full length precursor molecule , progastrin ( PG ) ( 1 80 ) , ( recombinant human PG ) in IEC cells . ^^^ To examine whether c Src kinase mediates proliferative effects of PG , IEC cells were microinjected with anti Src IgG and ( 3 ) H thymidine ( ( 3 ) H Tdr ) uptake of the cells measured . ^^^ These results suggest that activation of c Src kinase likely represents a critical step in mediating proliferative effects of both the precursor and fully processed forms of gastrins on IEC . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This activity depends on the membrane recruitment and activation of c Src kinase , thus uncovering a new role in endosome function . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Activation of STAT 3 requires the intrinsic kinase activity of RET / PTC ; Janus tyrosine kinase and c Src kinase are not involved in the RET / PTC mediated activation of STAT 3 . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
A significant correlation was shown between c Src kinase protein and cell invasion . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
While PLD activity as a lipid hydrolyzing enzyme is not affected by c Src , wild type PLDs but not catalytically inactive PLD mutants significantly increase c Src kinase activity , up regulating c Src mediated paxillin phosphorylation and extracellular signal regulated kinase activity . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Protein immunoprecipitation and kinase phosphorylation were employed to measure c Src kinase activity ; MAPK kinase activity was assessed by the phosphorylation rate of the substrate MBP ( Myelin Basic Protein ) ; Western blot was used to assess the protein expression of c Src and c fos . ^^^ RESULTS : c Src protein expressions in VSMC , which were transfected with different concentrations of anti sense c Src ODNs , were significantly decreased in a negative dose effect manner ( 0 . 2 microm , 0 . 5 microm , 1 . 0 microm and 2 . 0 microm were 68 . 2 % , 34 . 7 % , 30 . 3 % and 15 . 8 % respectively compared with control ) . c Src kinase activity was also obviously inhibited . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To elucidate the molecular mechanisms by which human epidermal growth factor receptor / heregulin ( HER2 / HRG ) influence the migratory potential of breast cancer cells , we have used phospho specific antibodies against c Src kinase and focal adhesion kinase ( FAK ) . ^^^ This study establishes that HER2 / HRG signaling selectively upregulates Tyr phosphorylation of c Src at Tyr 215 located within the SH 2 domain , increases c Src kinase activity and selectively upregulates Tyr phosphorylation of FAK at Tyr 861 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Phosphotransferase activities of Src kinase were also induced in the glucosylceramide depleted cells . c Src kinase activity and phosphorylations at Src Tyr 418 and epidermal growth factor ( EGF ) receptor Tyr 1068 were significantly enhanced by bradykinin in response to 100 nm D t EtDO P 4 compared with control cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
However , in vitro , Fak and Jak 2 kinases were not directly inhibited by PP 1 , demonstrating the effect of PP 1 on c Src kinase as an upstream activator of Fak . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Exposure to Zn ( 2+ ) , but not EGF , induced phosphorylation of the activating site of c Src ( tyrosine 416 ) , and Zn ( 2+ ) induced phosphorylation of EGFR at tyrosines 845 and 1068 was blocked by the c Src kinase activity inhibitor PP 2 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This work is based on our striking evidence that , in neuronal cells , nanomolar concentrations of alpha tocotrienol , but not alpha tocopherol , block glutamate induced death by suppressing early activation of c Src kinase ( Sen , C . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Both p130Cas and c Cbl have been reported to play critical roles in osteoclast function as downstream targets of c Src kinase . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Estrogen induced cell survival , but not E 2 dependent cell cycle progression , can be prevented by an inhibitor of c Src kinase or by blockade of the mitogen activated protein kinase kinase / extracellular signal regulated kinase signaling pathway . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Disruption of Ca2+ dependent cell matrix adhesion enhances c Src kinase activity , but causes dissociation of the c Src / FAK complex and dephosphorylation of tyrosine 577 of FAK in carcinoma cells . ^^^ Interestingly , both the in vivo level of Src [ pY 418 ] and in vitro c Src kinase activity were increased in carcinoma cells following disruption of Ca ( 2+ ) dependent cell matrix adhesion . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CONCLUSIONS : A c Src kinase inhibitor represses u PAR expression and , alone or in combination with a u PAR antagonist , diminishes colon cancer invasiveness . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Involvement of c Src kinase in the regulation of TGF beta 1 induced apoptosis . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CEACAM 6 overexpressing clones exhibited increased Akt and c Src kinase activities , as well as higher levels of matrix metalloproteinase 2 ( MMP 2 ) expression and activity in the presence of IGF 1 . ^^^ While Akt kinase is both necessary and sufficient to induce IGF IR upregulation , c Src kinase activity is necessary , but alone is insufficient to upregulate IGF IR expression . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Each of the stable cell lines in which kinase defective mutants of c Src were expressed had reduced levels of Bcl 10 ( L . ) However , inhibition of c Src kinase activity by PP 2 in vector control cells did not alter the oxaliplatin response over 72 h nor did it reduce Bcl 10 ( L ) levels . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Both omeprazole and TCDD dependent AhR signalling was attenuated by inhibition of c src kinase , either by using pyrazolopyrimidine 4 amino 5 ( 4 methylphenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 ] pyrimidine ( PP 1 ) and 4 amino 5 ( 4 chlorophenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyrimidine ( PP 2 ) inhibitors or by expression of dominant negative c src . ^^^ These results indicate that the overall AhR function is modulated by c src kinase activity . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The calcium channel currents were attenuated by 50 + / 3 % by the c src kinase specific inhibitor , PP 2 , in control cells but only 19 + / 7 % in cells from inflamed mice . ^^^ These studies suggest that decreased calcium channel currents following colonic inflammation are not due to decreased expression but may result from altered regulation by the non receptor cellular tyrosine kinase , c src kinase . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
They also act as transducers of signaling by recruiting c Src kinase to certain GPCRs . ^^^ Together , our results support a role for c Src in regulating the dissociation of AP 2 from agonist occupied AT1R and beta arrestin during the clathrin mediated internalization of receptors and suggest a novel function for c Src kinase in the internalization of AT1R . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Unlike the highly homologous cellular c Src kinase , a C terminal deletion of the regulatory tail and numerous point mutations make the viral kinase uncontrollable . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition to the sensitivity of ERKs to cytoskeletal integrity , GnRH induced FAK and c Src kinase activation were sensitive to these agents and the fibronectin integrin antagonistic RGDS peptide . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
PTPepsilonM activated c Src kinase probably by directly dephosphorylating phospho Tyr 527 , a negative regulatory site of c Src . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The treatment with c Src kinase inhibitor suppressed pressure induced proliferative response . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition , pyk 2 ( K457A ) blocked acid activation of c Src kinase , which is also required for acid regulation of NHE 3 . ^^^ The present results demonstrate that Pyk 2 is directly activated by acidic pH and that Pyk 2 activation is required for acid activation of c Src kinase and NHE 3 . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Studies on the mechanism of rapid activation of protein tyrosine phosphorylation activities , particularly c Src kinase , by TCDD in MCF10A . ^^^ These results support the conclusion that c Src kinase is at least one of the earliest and the most upstream components of toxic signaling of the Ah receptor activated by TCDD through the post transcriptional process . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
TCDD causes suppression of growth and differentiation of MCF10A , human mammary epithelial cells by interfering with their insulin receptor signaling through c Src kinase and ERK activation . ^^^ To test the hypothesis that TCDD induced c Src kinase activation is casually related to this compound ' s antagonistic action against insulin , we treated MCF10A cells with two c Src blocking agents , an anti Src antisense oligonucleotides blocker and a known specific inhibitor of c Src kinase , PP 2 and studied the effect of insulin and TCDD on cell proliferation . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
While c Src augmented IL 1 induced IKK activation independent of its kinase activity , the region comprising amino acids 361 440 in the c Src kinase domain are required for NF kappa B activation . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Our current work identifies two major targets of tocotrienol in the neuron : c Src kinase and 12 lipoxygenase . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
These novel treatments include an expanding array of drugs that primarily inhibit osteoclastic bone resorption ; oestrogenic compounds , bisphosphonates , inhibitors of receptor activator of nuclear factor kappaB ligand signalling , cathepsin K inhibitors , c src kinase inhibitors , integrin inhibitors and chloride channel inhibitors . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Biochemical assays performed in ipsilateral L4 / L5 dorsal root ganglia obtained following FCA / wild type ODN treatment showed : ( 1 ) an inhibition of the activity of c Src kinase , a member of the non receptor tyrosine kinase super family , ( 2 ) a decreased level of p 65 NF ( kappa ) B subunit , and ( 3 ) an inhibition of cyclooxygenase 2 ( COX 2 ) protein expression , a major pro inflammatory enzyme transcriptionally controlled by NF ( kappa ) B . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
D QSAR studies on c Src kinase inhibitors and docking analyses of a potent dual kinase inhibitor of c Src and c Abl kinases . ^^^ Three dimensional quantitative structure activity relationship ( 3D QSAR ) analyses were carried out on quinazoline , quinoline , and cyanoquinoline derivatives inhibiting c Src kinase . ^^^ In addition , a homology model of c Src kinase with the activation loop resembling the active conformation was constructed using the crystal structure of the kinase domain of Lck . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Analysis of the VEGF signaling pathway showed that Ad mda 7 inhibited c Src kinase activity and abrogated STAT 3 binding to the VEGF promoter . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In contrast , pharmacologic inhibition of endogenous c Src kinase activity or small interfering RNA mediated `` knockdown ' ' of c Src expression in L3 . 6pl cells with high Src expression and activity caused significant decreases in IL 8 production ( P < 0 . 005 ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This event is also essential for complete PDGF induced activation of c Src kinase by Tyr 416 phosphorylation , and the involvement of c Src kinase on H2O2 induced PDGFr tyrosine phosphorylation is demonstrated , suggesting a role of this kinase on the redox regulation of PDGFr activation . ^^^ Therefore , we suggest a redox circuit whereby , upon PDGF stimulation , PKC , PI3K and NADPH oxidase activity contribute to complete c Src kinase activation , thus promoting maximal phosphorylation and activation of PDGFr tyrosine phosphorylation . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
BACKGROUND AND PURPOSE : The current work is based on our previous finding that in neuronal cells , nmol / L concentrations of alpha tocotrienol ( TCT ) , but not alpha tocopherol ( TCP ) , blocked glutamate induced death by suppressing early activation of c Src kinase and 12 lipoxygenase . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Here we report three crystal structures of a dimeric active c Src kinase domain , in an apo and two ligand complexed forms , with resolutions ranging from 2 . 9A to 1 . 95A . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
New heterocyclic analogues of 4 ( 2 chloro 5 methoxyanilino ) quinazolines as potent and selective c Src kinase inhibitors . ^^^ A series of 5 , 7 disubstituted quinazolines , bearing 4 heteroaryl substituents such as 2 pyridinylamine or 2 pyrazinylamine , has been synthetised and evaluated as c Src kinase inhibitors . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Antagonists of TCDD which were found to be effective in this way were ( a ) inhibitors of c Src kinase , such as PP 2 and CGP 77675 , ( b ) those known to block the action of TGF alpha , such as anti TGF alpha antibody , and alpha ( 1 ) antitrypsin , ( c ) PD 98059 , a specific inhibitor of ERK activation , but not SB 202190 ( an inhibitor of p 38 MAPK activation ) or SP 600125 ( a JNK inhibitor ) and ( d ) Ah receptor antagonists , alpha naphthoflavone and 1 , 10 phenanthroline . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The stimulation of neutrophil like differentiated HL 60 cells with TNF alpha induced activation of NFkappaB and c Src kinase , and the activation was attenuated by treatment with the anti oxidants . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
First , CD 21 activation triggered Cbl tyrosine phosphorylation , which required c Src kinase but not PI 3 kinase or Syk kinase activities . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
As a lead compound , AP 23846 is a potent c Src kinase inhibitor ( IC 50 approximately 0 . 5 nmol / L in vitro , approximately 10 fold more potent than PP 2 , the most widely used commercially available Src family kinase inhibitor ) . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The findings point to an antioncogenic role for CD 99 in osteosarcoma , likely through the regulation of caveolin 1 and inhibition of c Src kinase activity . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We also review the effects of perturbation of endochondral ossification through four mechanisms inhibition of vascular endothelial growth factor ( VEGF ) , pp 60 c Src kinase and matrix metalloproteinases as well as disruption of the blood supply with vascular targeting agents . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
When cells are treated with Ca ( 2+ ) and Ca ( 2+ ) ionophore , c Src kinase activity increases , whereas c Yes kinase activity decreases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Among chemical inhibitors of signaling molecules , U 73122 ( phospholipase C ( PLC ) inhibitor ) , G6976 ( protein kinase C ( PKC ) inhibitor ) , BAPTA AM ( calcium chelator ) , LFM A 13 ( Bruton ' s tyrosine kinase ( Btk ) specific inhibitor ) , and PP 2 ( c Src kinase inhibitor ) suppressed AmB induced phosphorylation of p 65 and translocation of p 65 into the nucleus . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The role of c Src kinase in the regulation of osteoclast function . ^^^ Although it has been reported that restoring only the c Src adaptor function at least partly rescues the skeletal phenotypes , the importance of c Src kinase activity remains controversial . ^^^ Thus , c Src kinase activity not only on the plasma membrane but also within mitochondria is essential for the regulation of osteoclastic bone resorption . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The study of c Src kinase and pStat 3 protein expression in retinoblastoma . ^^^ We examine the immunoreactivity of the non receptor tyrosine kinase , c Src kinase and its downstream molecule , signal transducer and activator of transcription 3 ( pStat 3 ) in retinoblastoma ( RB ) , and correlation with invasiveness and differentiation . ^^^ The immunoreactivity of c Src kinase and pStat 3 was compared in the two groups of tumors . ^^^ Group 1 ( non invasive ) RB showed intermediate c Src kinase immunoreactivity ( Allred score 4 5 ) in 14 / 18 tumors and low immunoreactivity ( Allred score 2 3 ) in 4 / 18 tumors . pStat 3 was intermediate ( Allred score 4 5 ) in 6 / 18 tumors and negative ( Allred score 0 ) in 12 / 18 tumors . ^^^ Group 2 ( invasive ) RB showed high c Src kinase immunoreactivity ( Allred score 6 8 ) in 22 / 22 tumors and high pStat 3 ( Allred score 6 8 ) in 19 / 22 tumors . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The c src tyrosine kinase ( CSK ) gene , a potential antioncogene , localizes to human chromosome region 15q23 q 25 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CSK : a protein tyrosine kinase involved in regulation of src family kinases . ^^^ Recently we have purified and cloned a protein tyrosine kinase ( designated as CSK ) that can specifically phosphorylate the negative regulatory site of p60c src . ^^^ To elucidate the relationship between CSK and other types of src family kinases , we investigated the tissue distribution of CSK and examined whether CSK could phosphorylate the negative regulatory sites of src family kinases other than p60c src . ^^^ Western blot analysis indicated that CSK was enriched at the highest level in lymphoid tissues in which the expression of p60c src is considerably lower than those of other types of src family kinases . ^^^ The putative regulatory site , tyrosine 508 , was found to be essential for phosphorylation in p56lyn , and the kinase activities of these src family kinases were repressed by phosphorylation with CSK . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
P 3 was evaluated in vitro as an inhibitor of four different protein tyrosine kinases ( Src , Csk , EGF receptor , and FGF receptor ) and two protein serine kinases ( PK A and PK C ) . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The crystal structure of the SH 3 domain of Csk ( c Src specific tyrosine kinase ) has been refined at a resolution of 2 . 5 A , with an R factor of 22 . 4 % . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
A structural basis for the association of Csk with Src family members is also suggested from these studies . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The amino acid sequence of Ctk was found to possess 53 % identity with mouse Csk , shared all the predicted structural features of Csk , and was capable of phosphorylating the carboxyl terminal conserved tyrosine of Src family members . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Molecular cloning of lsk , a carboxyl terminal src kinase ( csk ) related gene , expressed in leukocytes . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CSK and TPK IIB once resolved from each other by heparin Sepharose affinity chromatography , display opposite specificities toward synthetic peptides reproducing the sequences around the main phosphoacceptor residues of pp60c src , namely Tyr 416 and Tyr 527 . ^^^ Spleen protein tyrosine kinases TPK IIB and CSK display different immunoreactivity and opposite specificities toward c src derived peptides . ^^^ Polyclonal antibodies have been raised against two synthetic peptides reproducing the 48 64 and 353 369 sequences of CSK , a protein tyrosine kinase implicated in the down regulation of src related protein kinases . ^^^ Both antibodies specifically recognize recombinant CSK and a CSK related 49 kDa protein tyrosine kinase present in spleen but they do not cross react with purified TPK IIB , a spleen protein tyrosine kinase sharing with CSK catalytic activity toward src kinases and incapability to autophosphorylate . ^^^ These data support the view that TPK IIB and CSK may exert opposite effects on the activity of src related protein tyrosine kinases . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In cells lacking the regulatory kinase ( CSK ) that phosphorylates tyrosine 527 , c Src is also found predominantly in focal adhesions , confirming that phosphorylation of tyrosine 527 affects the location of c Src inside the cell . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Mitotic activation of c Src is suppressed by Csk . ^^^ The overexpression of wild type Csk caused significant suppression of the c Src activity during mitosis . ^^^ A membrane targeted Csk , which has an amino terminal myristylation signal of c Src , exhibited an effective suppression of the c Src activity , even though its expression level was lower than that of endogenous Csk . ^^^ In contrast , the Csk deficient cells exhibited constitutive activation of c Src , which showed no significant change in its activity during mitosis . ^^^ These results suggest that Csk indeed participates in the regulation of the c Src activity during mitosis . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk is a non receptor protein tyrosine kinase that acts as a negative regulator of Src family tyrosine kinases . ^^^ On surveying several proteins known as Src substrates , we found that phosphorylation level of p80 / 85 ( cortactin ) was markedly elevated in the Csk deficient cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Evaluation of the catalytic mechanism of recombinant human Csk ( C terminal Src kinase ) using nucleotide analogs and viscosity effects . ^^^ In this study , we have investigated the tyrosine kinase reaction catalyzed by purified human recombinant Csk ( C terminal Src kinase ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk suppression of Src involves movement of Csk to sites of Src activity . ^^^ Csk phosphorylates Src family members at a key regulatory tyrosine in the C terminal tail and suppresses their activities . ^^^ To examine the features of Csk required for Src suppression , we expressed Csk mutants in a cell line with a disrupted csk gene . ^^^ Expression of wild type Csk suppressed Src , but Csk with mutations in the SH 2 , SH 3 , and catalytic domains did not suppress Src . ^^^ Whereas Src repressed by Csk was predominantly perinuclear , the activated Src in cells lacking Csk was localized to structures resembling podosomes . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Rapid and efficient purification of Src homology 2 domain containing proteins : Fyn , Csk and phosphatidylinositol 3 kinase p 85 . ^^^ To analyse the regulation of Src family tyrosine kinases in vitro , we have purified Fyn and Csk , a kinase capable of regulating Fyn activity by phosphorylation , from baculovirus infected insect cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Paxillin has also been implicated in cell signaling by virtue of its association with the protein tyrosine kinases pp60src and Csk ( C terminal Src kinase ) as well as with the adapter / oncoprotein p47gag crk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk type protein tyrosine kinase ( Ctk ) is a protein tyrosine kinase with structural and functional similarities to C terminal Src kinase ( Csk ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We demonstrate that the K protein contains a cluster of at least three SH 3 binding sites ( P 1 , PPGRGGRPMPPSRR , amino acids 265 278 ; P 2 , PRRGPPPPPPGRG , 285 297 ; and P 3 , RARNLPLPPPPPPRGG , 303 318 ) and that each one of these sites is capable of selectively engaging c Src and Vav SH 3 domains but not SH 3 domains of Abl , p 85 phosphatidylinositol 3 kinase , Grb 2 , and Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Although N Src was readily down regulated by Csk when coexpressed in yeast , it showed much higher specific activity than c Src , even in the repressed form . ^^^ Regulation of Src family kinases in the developing rat brain : correlation with their regulator kinase , Csk . ^^^ We have so far suggested that the functions of Src family protein tyrosine kinases are under the control of their regulator kinase , Csk . ^^^ To evaluate the role of Csk mediated regulation in neural tissues , we examined the correlation between the activities of Src family kinases and the expression level of Csk during development of the rat brain . ^^^ Consistent with the decrease in the Csk level , the kinase activity of a member of the Src family , Fyn , was greatly enhanced , but that of Src was not correlated inversely with the level of Csk expression . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Despite some differences in basal Src activity in the clones analyzed , Src activity was not significantly suppressed , while the amount of p50csk and Csk activity increased at least 10 fold during 3 days of induction . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The elevated expression of CSK in human colorectal cancer cell lines appeared to correspond to the elevated p60c src ( c Src ) and p62c yes ( c Yes ) protein tyrosine kinase activities found in other studies . ^^^ C terminal src kinase ( CSK ) is a cytoplasmic protein which decreases activities of the Src family protein tyrosine kinases . ^^^ Thus , CSK may not have an anti oncogenic role to play through the negative regulation of Src family kinases in colorectal carcinogenesis . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Phosphorylation of paxillin on tyrosine creates binding sites for the SH 2 domains of Crk , Csk , and Src . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To determine the role of the src family of nonreceptor protein tyrosine kinases , Csk ( for carboxyl terminal src kinase ) , a physiologic inhibitor of these kinases , was overexpressed in OKP cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk inhibition of c Src activity requires both the SH 2 and SH 3 domains of Src . ^^^ Src proteins mutated in either the SH 2 or SH 3 domain were as lethal as wild type c Src , but were insensitive to Csk , even though they were substrates for Csk in vivo . ^^^ Src proteins mutated in either the SH 2 or SH 3 domain were as lethal as wild type c Src , but were insensitive to Csk , even though they were substrates for Csk in vivo . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Mouse embryos lacking Csk , a negative regulator of Src family kinases , exhibit defects in neurulation and die at mid gestation . ^^^ To determine the role of activated Src family kinases in the csk phenotype , we have introduced mutations in the src and fyn genes into the csk mutant background . ^^^ Genetic analysis reveals that src , but not fyn , is partly epistatic to the csk gene . ^^^ Furthermore , the src mutation can restore the normal distribution of cortactin and partly correct filamentous actin organization in csk cells . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Paxillin physically complexes with two protein tyrosine kinases , pp60src and Csk ( COOH terminal src kinase ) , and the oncoprotein p47gag crk , each of which could function as part of a paxillin signaling complex . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In this study , we show that a peptide containing the unnatural amino acid trifluorotyrosine shows remarkably similar efficiency as a substrate of the tyrosine kinase Csk ( C terminal Src kinase ) compared with the corresponding tyrosine containing peptide despite a 4 unit change in the phenolic pKa . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Phosphorylation of Src mutants at Tyr 527 in fibroblasts does not correlate with in vitro phosphorylation by CSK . ^^^ The tyrosine kinases that phosphorylate Src at Tyr 527 in vivo have not been identified , but a tyrosine kinase known as CSK is an excellent candidate . ^^^ CSK has the unusual ability to phosphorylate Src in vitro only at Tyr 527 . ^^^ To examine whether CSK has the appropriate sequence specificy to explain the phosphorylation of Src at Tyr 527 in fibroblasts , we have made use of a set of C terminal substitution mutants of Src . ^^^ The ability of CSK to phosphorylate selected mutants has now been tested , using both in vitro phosphorylation assays and co expression of CSK with the Src mutants in a heterologous organism , Saccharomyces cerevisiae . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The C terminal src kinase ( Csk ) is responsible for the phosphorylation of the carboxy terminal tyrosine of several tyrosine kinases of the Src family . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Disruption of the csk gene , encoding a negative regulator of Src family tyrosine kinases , leads to neural tube defects and embryonic lethality in mice . ^^^ These results demonstrate that Src family kinase activity is critically dependent on phosphorylation by Csk and suggest that the regulation of kinase activity may be essential during embryogenesis . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
HYL has unique structural features shared with CSK ( C terminal Src kinase ) . ^^^ These findings establish close relationship between the HYL and CSK genes and also suggest that HYL may play an important role in signal transduction through SRC family kinases in the central nervous system . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We find that both the SH 2 and SH 3 domains are needed for inhibition of Src by Csk . ^^^ The SH 3 domain is needed for Src to be inhibited when Tyr 527 is phosphorylated by Csk . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We have used budding yeast to study the regulation of c Src activity by CSK in intact cells . ^^^ Coexpression of CSK in these cells results in phosphorylation of c Src on Y 527 and suppression of the c Src phenotype . ^^^ CSK does not fully suppress the activity of c Src mutants lacking portions of the SH 2 or SH 3 domains , even though these mutant proteins are phosphorylated on Y 527 by CSK both in vivo and in vitro . ^^^ C terminal Src kinase ( CSK ) is a candidate for the enzyme that catalyzes this phosphorylation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Biochemical and site directed mutagenesis analyses revealed that a carboxy terminal peptide of p54rak was phosphorylated by a cytoplasmic tyrosine kinase ( CSK ) and that , as in the Src family , it is the COOH terminal tyrosine that is phosphorylated by CSK . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We also show that the HS 1 peptide can be used for the specific monitoring of p72syk since neither the two Src related c Fgr and Lyn kinases ( needing a hydrophobic instead of acidic residue at position 1 ) nor CSK appreciably phosphorylate it . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In view of its homology to Csk , a negative regulator of Src family tyrosine kinases , and its generalized expression in the adult brain , we suggest that Batk may function as a brain specific regulator of kinases involved in the development and maintenance of the nervous system . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Comparison of the structure of BTK with that of other nonreceptor tyrosine kinases , including SRC , FES , and CSK , demonstrated a lack of conservation of exon borders . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Phosphorylation by Cdc 2 partially reactivated Csk inactivated pp60c src . ^^^ Moreover , phosphorylation of Csk treated pp60c src by Cdc 2 also facilitated complete reactivation by the protein tyrosine phosphatase CD 45 or by a synthetic phosphopeptide corresponding to the C terminal , regulatory phosphorylation site ( Tyr 527 ) . ^^^ These data indicate that the Src homology 2 domain of Csk phosphorylated pp60c src was more accessible for intermolecular interactions and that Tyr 527 was more readily dephosphorylated after treatment with Cdc 2 . ^^^ Following complete dephosphorylation , purified p60c src was rephosphorylated with Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The kinase activity of the Src family of PTKs is negatively regulated by phosphorylation at the C terminal tyrosine residue , and the PTK Csk has been demonstrated to phosphorylate this C terminal residue of the Src family of PTKs . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We have shown that suppression of a certain fraction of c Src activity by Csk may require the binding of Csk to tyrosine phosphorylated paxillin . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Lsk is a protein tyrosine kinase with homology to the COOH terminal Src kinase ( Csk ) . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Paxillin is tyrosine phosphorylated during interphase of the cell cycle by protein tyrosine kinases ( PTK ) such as c Src and Csk , and becomes dephosphorylated during mitosis . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The location of intron / exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub families of intracellular PTKs , namely that of Src , Fes / Fer , Csk , and Abl / Arg . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Src proteins mutated in the SH 2 domain were as lethal as wild type Src , but were insensitive to Csk . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk , which phosphorylates tyrosine residues in the negative regulatory sites of Src family kinases , down regulated Fyn and Lck mediated stimulation of the serum response element and Fyn mediated enhancement of IL 2 promoter activity . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Regulation of Src family tyrosine kinases by Csk ] . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Constitutive activation of Src family kinases in mouse embryos that lack Csk . ^^^ Csk is a novel cytoplasmic protein tyrosine kinase that has been shown to inactivate members of the Src family of protein tyrosine kinases in vitro . ^^^ Thus , these results suggest that Csk indeed acts as an indispensable negative regulator of Src family kinases in vivo . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Key elements in these reactions are members of the Src , Syk and Csk families of protein tyrosine kinases ( PTKs ) and the phosphotyrosine phosphatases ( PTPases ) that regulate and / or counteract them , such as CD 45 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Expression of the COOH terminal Src kinase ( Csk ) , which represses Src kinases , also blocked induction of c fos transcription by ET 1 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Inducible expression of c Src in fission yeast is lethal unless Csk is coexpressed . ^^^ Structural requirements for the efficient regulation of the Src protein tyrosine kinase by Csk . ^^^ Mutagenesis of the SH 3 and SH 2 domains of Csk show that neither are necessary in yeast or in vitro for efficient regulation of Src . ^^^ The residual activity of full length Src mutated at Tyr 416 is efficiently repressed by Csk action , suggesting that regulation by C terminal phosphorylation does not act by preventing phosphorylation at Tyr416 . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Immunofluorescence microscopy revealed that multiple signaling molecules ( e . g . , pp60c src , pp125FAK , phosphatidylinositol 3 kinase , phospholipase C gamma , and Na+ / H+ antiporter ) involved in both integrin and growth factor receptor signaling pathways became associated with the CSK framework of the FAC within 15 min after binding to beads coated with integrin ligands . ^^^ Western blot analysis confirmed that FACs isolated using RGD beads were enriched for pp60c src , pp125FAK , phospholipase C gamma , and the Na+ / H+ antiporter when compared with intact CSK or basal cell surface preparations that retained lipid bilayer . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Lyn and c Fgr phosphorylated by C terminal Src kinase ( CSK ) at their down regulatory site are resistant to the action of both PTPases while the [ Phe 6 ] Src ( 514 533 ) phosphopeptide , representing the highly similar site affected by CSK in c Src , is readily dephosphorylated by both PTPases , although to a different extent . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The protein tyrosine kinase Csk is one of the main down regulators of the Src family of kinases . ^^^ Csk may be involved in the down regulation of T cell receptor ( TCR ) signaling by C terminal tyrosine phosphorylation of Lck and Fyn ; however , it is not known how Csk activity is regulated or how it targets these Src family members . ^^^ In both Jurkat and normal T cells , the Src homology 2 ( SH 2 ) domain of Csk bound constitutively to a tyrosine phosphorylated protein of 60 kDa ( p 60 ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The COOH terminal Src kinase ( Csk ) is responsible for the phosphorylation of the conserved , negative regulatory , carboxyl terminal tyrosine of most of the Src family protein tyrosine kinases . ^^^ Up to now , no stable binding of Csk to Src kinases has been detected . ^^^ First , using real time biospecific interaction analysis ( BIAcore ( TM ) ) , we detected in vitro a specific interaction between Csk and one of its substrates Lck , a lymphocyte specific member of the Src family . ^^^ These findings might explain the mechanism ( s ) by which Csk interacts with most of Src kinases to down regulate their kinase activity . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Protein tyrosine kinases of the Syk , Src and Csk families and the CD 45 protein tyrosine phosphatase ( PTPase ) are known to be involved in these early biochemical reactions . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In contrast , adhesion induced tyrosine phosphorylation of Cas was reduced in cells lacking Src , whereas enhanced phosphorylation of Cas was observed Csk cells , in which Src kinases are activated . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In the genistein pretreated platelets , pp 60 ( c ) src , Gq , and protein kinase Calpha were no longer able to associate with CSK . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Downregulation of Src family kinases by the C terminal Src kinase ( Csk ) suppressed Btk * activation and biological potency . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CHK / HYL is a non receptor tyrosine kinase that belongs to CSK ( C terminal Src kinase ) family . ^^^ CHK / HYL did not affect the activity of Src , Hck , and Fgr in cultured bone marrow cells , although CSK negatively regulates Src family kinases . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Src family of protein tyrosine kinases and their regulator tyrosine kinase , Csk ] . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Src peptide and its derivatives were tested as inhibitors of three non receptor tyrosine kinases ( Lyn , belonging to the Src family , CSK and PTK IIB ) and a non receptor protein tyrosine phosphatase obtained from human T cell ( TC PTP ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
RPDE 6 exhibited selectivity in binding to the SH 3 domains of c Abl , Crk , Csk , Lck , Lyn , Fyn and 5 Src , with binding to the SH 3 regions of the Src related tyrosyl kinases Lyn and Fyn being the most effective . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Purification of bovine thymus cytosolic C terminal Src kinase ( CSK ) and demonstration of differential efficiencies of phosphorylation and inactivation of p56lyn and pp60c src by CSK . ^^^ With this assay method , we demonstrated that CSK inactivated p56lyn with a significantly higher efficiency than pp60c src . ^^^ Phosphopeptide mapping of CSK phosphorylated p56lyn and pp60c src shows that the consensus tyrosine residue ( also termed tail tyrosine ) in the C terminal regulatory domain of p56lyn was phosphorylated by CSK with an efficiency much higher than that of pp60c src . ^^^ The synthetic peptides derived from the C terminal portion of p56lyn and pp60c src were much poorer substrates than the intact src family kinases for CSK , indicating that the local structure around the tail tyrosine is not sufficient to direct efficient phosphorylation of p56lyn by CSK . ^^^ Nevertheless , the slightly higher efficiency displayed by CSK in phosphorylating the peptide derived from the C terminal portion of p56lyn than that from pp60c src suggests that the structural differences between the C terminal portions of p56lyn and pp60c src contribute to the differential efficiencies displayed by CSK in phosphorylating the two kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We previously showed that Csk is a potent negative regulator of antigen receptor signaling in T lymphocytes and that its Src homology ( SH ) 3 and SH 2 domains are required to inhibit these signals . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
An association between active Cdc 2 and the Src related kinases Lyn and Fyn was also demonstrated , although Cdc 2 was not found associated with the tyrosine kinases , Csk and Syk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Many intracellular pathways can be stimulated upon Src activation , and a variety of cellular consequences can result , including morphological changes and cell proliferation . pp60c src activity is normally suppressed by phosphorylation on its carboxy terminal tail by an enzyme known as CSK . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The C terminal Src kinase ( Csk ) is widely expressed , active in HT 29 cells that contain activated Src , and its expression is downregulated in butyrate treated SW 620 cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Like p50csk , Chk reduced the elevated phosphotyrosine levels and the augmented activity of Src family kinases in Csk deficient fibroblasts . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Csk homologous kinase ( CHK ) , formerly MATK , is a tyrosine kinase that contains the Src homology 2 and 3 ( SH 2 and SH 3 ) domains and demonstrates homology ( approximately 50 % ) to the Csk tyrosine kinase . ^^^ Like Csk , CHK is able to phosphorylate and inactivate Src family kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Lysophosphatidic acid stimulates binding of EGF receptor to a GST fusion protein containing the c Src SH 2 domain , and this too is blocked by Csk expression . ^^^ Expression of Csk , which inactivates Src family kinases by phosphorylating the regulatory carboxyl terminal tyrosine residue , has the same effect . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This activation was investigated in detail using purified Csk , Src , and the fibroblast growth factor receptor kinase , which led to the following conclusions . ( 1 ) The catalytic activity of these kinases is dependent on the Mg2+ concentration present in the assay , approaching saturation at 5 8 mM MgCl 2 , while ATP was saturated at approximately 1 mM MgCl 2 . ( 2 ) Extrapolation to zero free Mg2+ at a constant ATP Mg concentration predicts zero activity , suggesting that free magnesium ion in excess of that needed to bind to ATP is essential for the activation of these enzymes . ( 3 ) The free magnesium ion activates Csk and Src kinase activity by increasing the Vmax but does not change their apparent Km ( ATP Mg ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk ( C terminal Src kinase ) is a protein tyrosine kinase which catalyzes the transfer of the gamma phosphoryl group of ATP to the tyrosine hydroxyl of proteins in the presence of a divalent ion . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The catalytic activity of src family protein tyrosine kinases ( src PTK ) is suppressed when a C terminal tyrosine is phosphorylated by an intracellular PTK , C terminal Src kinase ( Csk ) . ^^^ Csk overexpression resulted primarily in a down regulation of Fgr activity , an src PTK expressed in J774A . 1 , and hyperphosphorylation of several cellular proteins of 35 , 57 , 66 , 97 and 120 130 kDa . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The cells were engineered to express Src along with Csk , a protein kinase able to phosphorylate Tyr 527 efficiently . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To examine the neural function of Csk ( C terminal Src kinase ) , a membrane targeted form of Csk ( Src / Csk ) and its kinase defective variant ( DK Src / Csk ) were expressed in the embryonic carcinoma cell line P 19 . ^^^ Expression of Src / Csk , but not DK Src / Csk , caused reduction of the specific activities of Src and Fyn in the differentiated P 19 cells . ^^^ During neural differentiation , the specific activity of Src was elevated in the control P 19 cells , whereas the activation was completely eliminated in the Src / Csk transfectant . ^^^ In the Src / Csk transfectant , L 1 stimulation induced delayed activation of Src and Fyn peaking at much lower levels than in the control cells . ^^^ Src / Csk transfectants developed normally in the initial stages of neural differentiation , but exhibited an apparent defect in cell to cell interaction , i . e . neurite fasciculation and aggregation of cell bodies , in the latter stages . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
These can be divided into nine families : Abl , Fes / Fer , Syk / Zap70 , Jak , Tec , Fak , Ack , Src , and Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Chk and Lyn , but not Csk and c Src , co fractionated in the higher density lysate fractions of resting platelets , with Chk being found to localize close to CD 36 ( membrane glycoprotein 4 ) anchored Lyn . ^^^ Chk / Hyl is a recently isolated non receptor tyrosine kinase with greatest homology to a ubiquitous negative regulator of Src family kinases , Csk . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Recent biochemical and genetic studies implicate Csk ( carboxy terminal Src kinase ) as the one of the main downregulators of the activity of members of the Src family of kinases . ^^^ Csk is probably involved in the downregulation of TCR signaling by C terminal tyrosine phosphorylation of Lck and Fyn , but the mechanism whereby Csk targets these Src family members is not known . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
An eicosapeptide encompassing the C terminal tail of c Src ( Tyr 527 ) which is conserved in most Src related protein kinases , is phosphorylated by C terminal Src kinase ( CSK ) and by the two Src related protein kinases c Fgr and Lyn , with similar kinetic constants . ^^^ Two related peptides reproducing the C terminal segments of c Src mutants defective in CSK phosphorylation [ MacAuley , A . , Okada , M . , Nada , S . , Nakagawa , H . & Cooper , J . ^^^ Sequence specificity of C terminal Src kinase ( CSK ) a comparison with Src related kinases c Fgr and Lyn . ^^^ A . ( 1993 ) Oncogene 8 , 117 124 ] AFLEDSCTGTEPLYQRGENL ( mutant number 28 ) and AFLEDNFTGTKPQYHPGENL ( mutant number 29 ) , proved a better and a much worse substrates , respectively than the wild type peptide , with either CSK or the two Src kinases . ^^^ By contrast to most peptide substrates , including the Src C terminal peptides , which exhibit relatively high K ( m ) values , a polyoma virus middle T antigen ( mT ) derived peptide with tyrosine embedded in a highly hydrophobic sequence ( EEEPQFEEIPIYLELLP ) exhibits with CSK a quite low K ( m ) value ( 63 microM ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
As an attempt to analyze the roles of C terminal Src kinase ( Csk ) in the high affinity IgE receptor ( FcepsilonRI ) mediated signaling , we overexpressed Csk , a membrane targeted form of Csk ( mCsk ) , and a kinase defective , membrane targeted form of Csk ( mCsk ( ) ) in rat basophil leukemia ( RBL ) 2H3 cells . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Finally , based on sequence alignments and conservation of hydrophobic residues in the Src SH 2 kinase linker as well as in the alphaC beta 4 and beta 2 beta3 loops , we propose that the Src related kinases , Abl , Btk and Csk , share the same quaternary structure . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Expression patterns of csk , a negative regulator of Src family kinase activities , were not consistent with its involvement in the differentiation dependent activation of p53 / 56lyn ; however , there was some indication of the participation of a tyrosine phosphatase in the regulation of p53 / 56lyn . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk ( C terminal Src kinase ) is a protein tyrosine kinase that phosphorylates Src family member C terminal tails , resulting in down regulation of Src family members . ^^^ In addition , a catalytically inactive version of the Src family member , Lck ( lymphoid cell kinase ) , was expressed , purified , and evaluated as a Csk substrate . ^^^ The high efficiency of purified Csk phosphorylating a pure , unphosphorylated Src family member argues against the importance of an SH 2 phosphotyrosine docking interaction or the involvement of extra recruitment proteins in facilitating Csk phosphorylation of Src family members . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk is a protein tyrosine kinase that phosphorylates other protein tyrosine kinases of the Src family and down regulates their activities . ^^^ We found that Csk was phosphorylated by the cAMP dependent protein kinase ( PKA ) , but not by protein kinase C , Src , or the fibroblast growth factor receptor kinase . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Overexpression of a dominant negative mutant of c Src or of the negative regulator of c Src function , Csk , results in attenuation of the alpha1B AR and alpha2A AR mediated Erk1 / 2 signals . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
One of them , soluble tyrosine kinase 1 ( STK 1 ) , represents a soluble form of the c Src protein , which is apparently underphosphorylated on its C terminal tyrosine residue whereas the other ( STK 2 ) is a 48 kDa protein tyrosine kinase ( PTK ) , which is molecularly and functionally related to the C terminal Src kinase ( Csk ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We previously demonstrated that , via its Src homology 3 ( SH 3 ) domain , Csk is tightly bound to PEP , a protein tyrosine phosphatase ( PTP ) exclusively expressed in hemopoietic cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
When CSK , a negative regulator of Src family tyrosine kinases , or dominant negative mutant of Ras or of Raf 1 kinase was overexpressed , activation of transfected ERK 2 by H2O2 was abolished . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Csk homologous kinase ( Chk ) , which is co expressed with C terminal Src kinase ( Csk ) in hematopoietic cells , negatively regulates Src family kinases in vitro with selectivity toward Lyn but not c Src in platelets . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Sequence requirements for association of protein tyrosine phosphatase PEP with the Src homology 3 domain of inhibitory tyrosine protein kinase p 50 ( csk ) . ^^^ This interaction was shown to involve the Src homology 3 ( SH 3 ) region of Csk and a proline rich sequence of PEP termed P 1 ( SRRTDDEIPPPLPERTPESFIVVEE ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
These responses were markedly reduced in cells overexpressing the Csk kinase or in cells that lack focal adhesion kinase or the Src family kinases Src or Fyn . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The kinases Abl , Btk and Csk seem to have the same molecular architecture as Src . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Csk homologous kinase ( CHK ) is a recently identified tyrosine kinase which , like Csk , phosphorylates the C terminal tyrosine of Src kinases , resulting in inactivation of these enzymes . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
BatK is a second member of the Csk family of regulatory kinases that phosphorylate a key inhibitory tyrosine on Src family kinases , leading to down regulation . ^^^ We propose a model suggesting that , despite overlapping in vitro activities , BatK and Csk regulate different targets in vivo and have different functions during and after neuronal development , BatK being the dominant regulator of Src kinases in the fully differentiated adult brain . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Kinase activity was only detectable in cancer cells and did not correlate with the amount of kinase protein or with the expression of the regulatory kinase Csk , indicating that Src is not regulated through protein expression or through expression of Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Overexpression of C terminal Src kinase ( Csk ) , which inactivates Src family tyrosine kinases , suppressed the activation of transfected ERK in cardiac fibroblasts . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Autophosphorylation of Src Tyr 416 correlates with enzyme activation , while phosphorylation of C terminal Tyr 527 by Csk gives rise to inactive forms of Src kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This method was used to ligate a phosphotyrosine peptide to the C terminus of the protein tyrosine kinase C terminal Src kinase ( Csk ) . ^^^ The semisynthetic tail phosphorylated Csk showed evidence of an intramolecular phosphotyrosine Src homology 2 interaction and an unexpected increase in catalytic phosphoryl transfer efficiency toward a physiologically relevant substrate compared with the non tail phosphorylated control . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Regulation of mouse PECAM 1 tyrosine phosphorylation by the Src and Csk families of protein tyrosine kinases . ^^^ Through reconstitution experiments in COS 1 cells , we determined that mouse PECAM 1 could be tyrosine phosphorylated by Src related PTKs and Csk related PTKs , but not by other kinases such as Syk , Itk , and Pyk 2 . ^^^ In other studies , we demonstrated that phosphorylation of PECAM 1 by Src or Csk family kinases was sufficient to trigger its association with SHP 2 . ^^^ Taken together , these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM 1 and triggering its association with SH 2 domain containing phosphatases under physiological circumstances . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Coexpression of Csk , which serves as a Src dominant interfering kinase , and constitutively active forms of Src , together with JNK , confirmed the involvement of c Src downstream of PKC in the GnRH JNK pathway . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The first class encodes for the protein tyrosine kinase Csk , known to regulate Src activity through phosphorylation of the C terminal tyrosine . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Microinjection of either anti Cst . 1 antibody or recombinant CSK , both of which prevent activation of Src family kinase , significantly decreases ATP induced activation of AE . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk is a cellular protein tyrosine kinase ( PTK ) that has been shown to specifically regulate the activity of Src kinase family members by phosphorylation of a carboxy terminal tyrosine residue . ^^^ However , an increased number of Csk substrates was detected in NIH3T3 cells expressing a constitutively activated form of the Src kinase Lck or in PC 12 and NIH3T3 cells that had been treated with pervanadate . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk is an important regulator of tyrosine kinases of the Src family . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Regulation of the src family of tyrosine kinases is mediated by the coordinated action of the tyrosine kinase Csk and the tyrosine phosphatase CD 45 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition , the Galpha 11 Q209L stimulated activation of both kinases was blocked by a specific inhibitor of protein tyrosine kinases ( PP 2 ) and Csk ( C terminal Src kinase ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Here we show that the inactivation of the negative regulator of Src family PTKs , carboxy terminal Src kinase ( Csk ) , in immature thymocytes abrogates the requirement for preTCR , alphabetaTCR and major histocompatibility complex ( MHC ) class 2 for the development of CD4+ 8+ double positive and CD4+ single positive thymocytes as well as peripheral CD 4 alphabetaT lineage cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The protein tyrosine kinase Csk downregulates the activity of the Src family of kinases and has a negative effect on signal transduction through several Src kinase associated receptors . ^^^ Because the Src family kinase Lyn plays a pivotal role in FcepsilonRI mediated cellular activation , we examined whether Csk is involved in FcepsilonRI signaling events . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Autophosphorylation of Src and Yes blocks their inactivation by Csk phosphorylation . ^^^ Csk phosphorylates Src family protein tyrosine kinases on a tyrosine residue near their C terminus and downregulates their activity . ^^^ We previously observed that this regulation requires a stoichiometric ratio of Csk : Src in a time independent manner . ^^^ First , pre incubation of Src with ATP Mg led to time dependent autophosphorylation of Src , activation of its kinase activity and loss of its ability to be inactivated by Csk . ^^^ However , the autophosphorylated Src can still be phosphorylated by Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition , paxillin , a Src and / or pp 125 ( FAK ) substrate , displayed increased levels of tyrosine phosphorylation in PTPalpha expressing cells and was associated with elevated amounts of Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
ET dependent stimulation of the human ANP gene promoter was partially inhibited by co transfection with dominant negative Ras or dominant negative Src or Csk or by treatment with the potent Src family selective tyrosine kinase inhibitor PP 1 , suggesting that the Src family kinases are involved in signaling ET dependent activation of this promoter . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition , like paxillin , Hic 5 can bind to a negative regulator of Src PTKs , csk but does not bind to the adaptor protein Crk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Previously , we reported that another PTK termed p 50 ( csk ) was a potent negative regulator of T cell receptor ( TCR ) signaling because of its ability to inactivate Src related kinases . ^^^ This inhibitory effect required the catalytic activity of Csk , as well as its Src homology ( SH ) 3 and SH 2 domains . ^^^ Through reconstitution experiments in Cos 1 cells , evidence was obtained that Csk and PEP act synergistically to inhibit protein tyrosine phosphorylation by Src related kinases , and that this effect requires their association . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The polypeptide chain fold of CSK is most similar to c Src , Hck and fibroblast growth factor receptor 1 kinase ( FGFR1K ) and most dissimilar to insulin receptor kinase ( IRK ) . ^^^ Structure of the protein tyrosine kinase domain of C terminal Src kinase ( CSK ) in complex with staurosporine . ^^^ The crystal structure of the kinase domain of C terminal Src kinase ( CSK ) has been determined by molecular replacement , co complexed with the protein kinase inhibitor staurosporine ( crystals belong to the space group P 21212 with a=44 . 5 A , b=120 . 6 A , c=48 . 3 A ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Adenovirus mediated overexpression of C terminal Src kinase ( Csk ) in type 1 astrocytes interferes with cell spreading and attachment to fibronectin . ^^^ To examine the role of C terminal Src kinase ( Csk ) , a negative regulatory kinase of Src family tyrosine kinases , in the cell adhesion mechanism of the nervous system , wild type Csk ( Csk ) , and a kinase deficient mutant of Csk ( Csk DeltaK ) were overexpressed in primary cultured type 1 astrocytes by infecting them with the recombinant adenovirus . ^^^ Overexpression of Csk repressed the in vitro kinase activity of Src to as little as 10 % that of control cells and interfered with cell spreading and cell attachment to fibronectin . ^^^ On the other hand , overexpression of Csk DeltaK induced tyrosine phosphorylation of cellular proteins , including the paxillin and focal adhesion kinase ( FAK ) and enhanced to some extent the cytoskeletal organization and the rate of cell spreading on fibronectin , indicating that Src or its relatives was functionally activated in the cells . ^^^ These findings suggest that Csk regulates Src family tyrosine kinases that play essential roles in the regulation of cell adhesion via a FAK dependent mechanism and that the tyrosine phosphorylation of paxillin alone may not be sufficient for the regulation of the cell adhesion mechanism in astrocytes . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
These results suggest that the reduced activity of tyrosine kinase of Csk may play an important role in the malignant transformation of hepatocytes in human and LEC rat , and the appearance of 53 kd Csk related protein may be closely involved in the progression of cirrhosis to HCC in humans , and that 50 kd Csk may act as an antioncogene through the negative regulation of pp 60 ( c src ) in the development of human HCC . . ^^^ Reduced C terminal Src kinase ( Csk ) activities in hepatocellular carcinoma . ^^^ C terminal Src kinase ( Csk ) is a novel cytoplasmic protein tyrosine kinase that inactivates the members of the Src family protein tyrosine kinase in vitro . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The results suggest that c Src and CSK are involved in IGF IR and IR signaling and that the interaction of CSK with the IGF IR may play a role in the decrease in c Src activity following IGF 1 stimulation . . ^^^ We observed that the IGF IR and IR associated with the C terminal Src kinase ( CSK ) following ligand stimulation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Clear evidence was found for the presence of N cadherin and its associated intracellular proteins : beta catenin , pp 120 , desmoglein , pp 60 ( src ) , and Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Analysis of LMP2A deletion mutants demonstrated that tyrosines implicated in interacting with Src family kinase SH 2 domains and the SH 2 domain of Csk , as well as the LMP2A immunoreceptor tyrosine based activation motif , are important for its phosphorylation in epithelial cells . ^^^ Instead , coexpression of Csk , a negative Src regulator , and LMP2A led to an increase in LMP2A phosphorylation both in nonadherent cells and upon cell adhesion . ^^^ Although tyrosine phosphorylation of LMP2A occurs in both cell types , different protein kinases seem to be used : Src family kinases in B lymphocytes and Csk in epithelial cells . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The phosphorylation of Src in IC8 . 1 cells reflected phosphorylation of the negative regulatory tyrosine 527 ( Y 527 ) ; thus , the inhibitor was selective against the Y 527 C terminal Src kinase Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Csk Homologous Kinase ( CHK ) has been shown to have an enzymatic activity similar to the tyrosine kinase Csk in that it down regulates Src family kinase activity by causing phosphorylation of the Src C terminal tyrosine residue . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Mutations in the N terminal regulatory region reduce the catalytic activity of Csk , but do not affect its recognition of Src . ^^^ To study its role , we introduced either deletion or site specific mutations within this region and analyzed the effect of such mutations on the catalytic activity of Csk and its ability to phosphorylate / inactivate Src protein tyrosine kinase , its physiological substrate in the cell . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Expression of Csk , which inactivates Src family kinases , totally inhibited gastrin induced Src like activity detected in anti Src and anti Shc precipitates but diminished by 50 % Shc phosphorylation and ERK 1 activation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
GEM in Neuro2a cells , separated as a low density membrane fraction , contains essentially all glycosphingolipids and sphingomyelin , together with five signal transducer molecules ( c Src , Lyn , Csk , Rho A , Ha Ras ) . ( 3 ) H Labeled Il ( 3 ) NeuAc LacCer ( GM 3 ) , Gb4Cer ( globoside ) , and Il ( 3 ) NeuAc Gg4Cer ( GM 1 ) added exogenously to cells were incorporated and concentrated in the low density GEM fraction . ^^^ In contrast , more than 50 % of glycerophospholipids and 30 % of cholesterol were found in the high density fraction . ( 3 ) H Labeled phosphatidylcholine added exogenously to cells was incorporated exclusively in the high density fraction . c Src , the predominant signal transducer in the microdomain , was coimmunoprecipitated with anti GM 3 antibody DH 2 or with anti Csk ; reciprocally , Csk was coimmunoprecipitated with anti c Src , indicating a close association of GM 3 , c Src , and Csk . ^^^ Brief stimulation of an isolated GEM fraction by the exogenous addition of GM 3 , but not lactosylceramide , caused enhanced c Src phosphorylation with a concomitant decrease of Csk level in GEM . ^^^ A decreased Csk / c Src ratio in GEM may cause activation of c Src because Csk is a negative regulator of c Src . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Using C terminal Src kinase ( Csk ) as a model system , we discuss progress in three main areas . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk ( C terminal Src kinase ) is a protein tyrosine kinase that phosphorylates Src family member C terminal tails , resulting in downregulation of Src family members . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The stimulatory EGFR signal is insensitive to inhibition of JAKs and appears to involve Src kinases and STAT proteins as shown by inhibition through overexpression of C terminal Src kinase ( Csk ) and transdominant negative STAT 3 , respectively . ^^^ Src kinases have been observed in association with the IL 6 receptor ; however , inhibition of Src kinases by Csk enhances IL 6 induced transcription . ^^^ The Csk effect is attributed to prevention of Src kinases from phosphorylating gp 130 at the docking site for the signal moderating protein tyrosine phosphatase SHP 2 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Src kinase activity is downregulated by the carboxy terminal Src kinase ( Csk ) , a tyrosine kinase that phosphorylates a conserved tyrosine residue in the carboxy terminal tail of Src [ 7 ] [ 8 ] . ^^^ Here , we report that loss of csk resulted in a reduction in the abundance of the Src and Fyn proteins , which could be restored by reintroducing catalytically active Csk . ^^^ The effect of Csk on Src expression was not due to an increase in Src message , but to stabilization of the Src protein . ^^^ Inhibition of proteasome activity also increased the level of Src protein in csk deficient cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To this end , we engineered OK cells to express the COOH terminal Src kinase ( Csk ) , a negative regulator of SFKs . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We constructed an adenovirus vector carrying the csk gene , which negatively regulates Src family tyrosine kinases . ^^^ Csk overexpression in cultured rheumatoid synoviocytes remarkably suppressed Src kinase activity and reduced their proliferation rate and IL 6 production . ^^^ In conclusion , adenovirus mediated direct transfer of the csk gene is useful in repressing bone destruction and inflammatory reactions , suggesting the involvement of Src family tyrosine kinases in arthritic joint breakdown and demonstrating the feasibility of intervention in the kinases for gene therapy in RA . off . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We screened 1680 spatially separated compounds of a diverse combinatorial library of 1 , 4 benzodiazepines for their ability to inhibit the kinase activity of protein tyrosine kinases Src , Yes , Abl , Lck , Csk , and fibroblast growth factor receptor . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Galpha12Q229L stimulated activation of JNK was blocked by a specific inhibitor of protein tyrosine kinases ( PP 2 ) , and C terminal Src kinase ( Csk ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Furthermore , Galphao * expression increased activity of the tyrosine kinase c Src , and the Galphao * induced activation of Stat 3 was blocked by expression of Csk ( carboxyl terminal Src kinase ) , which inactivates c Src . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
As the roles of tyrosine kinases such as focal adhesion kinase , c Src , and Csk in this pathway are being extensively studied , increasing evidence is emerging about the importance of protein tyrosine phosphatases ( PTP ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Because of suggestive evidence that 14 , 15 EET also activated Src in these cells , we stably transfected LLCPKcl 4 with an expression construct of the C terminal Src kinase ( CSK ) , which inhibits Src family kinase activity . ^^^ In vitro Src kinase activity assays confirmed that in empty vector transfected cells ( Vector cells ) , 14 , 15 EET increased Src kinase activity , while in clones overexpressing CSK mRNA and immunoreactive protein ( CSK cells ) , 14 , 15 EET induced activation of Src was almost completely blocked ( 94 % inhibition ) . ^^^ Of interest , epidermal growth factor ( EGF ) and fetal bovine serum ( FBS ) also increased Src activity in Vector cells , but not in CSK cells , further confirming the ability of CSK overexpression to prevent Src activation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In lymphoid cell lines and in resting peripheral blood alpha / beta T cells , PAG is expressed as a constitutively tyrosine phosphorylated protein and binds the major negative regulator of Src kinases , the tyrosine kinase Csk . ^^^ Expression of PAG in COS cells results in recruitment of endogenous Csk , altered Src kinase activity , and impaired phosphorylation of Src specific substrates . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Cbp is involved in the membrane localization of Csk and in the Csk mediated inhibition of c Src . ^^^ The activity of Src PTKs in cells of different types is negatively controlled by Csk , which specifically phosphorylates a conserved regulatory tyrosine residue at the carboxy terminal tail of the Src PTKs . ^^^ Csk is mainly cytoplasmic and Src PTKs are predominantly membrane associated . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
According to ( 1 ) its immunologic cross reactivity with the monoclonal anti cSrc antibody , m 327 , and with the N terminally directed monoclonal cSrc 2 17 antibody , ( 2 ) its inhibition by the C terminal cSrc kinase , CSK , and ( 3 ) its specificity for phosphorylating tyrosine 15 in the cdc 2 ( 6 20 ) peptide kinase substrate , we conclude that the kinase we have isolated represents porcine cSrc . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The proline , glutamic acid , serine and threonine enriched protein tyrosine phosphatase PEP , which is expressed primarily in hematopoietic cells , was recently discovered to be physically associated with the 50 kDa cytosolic protein tyrosine kinase ( PTK ) Csk , an important suppressor of Src family PTK , including Lck and Fyn in T cells . ^^^ Finally , we observed that PEP reduced c fos activation in a synergistic manner with Csk , supporting the notion that these two enzymes form a functional team acting on Src family kinases involved in TCR signaling . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Src / Csk regulatory circuit arose early in metazoan evolution . ^^^ Comparison of the expression pattern of Hydra Csk with that of STK , the Hydra Src gene orthologue , reveals that the two genes are largely co expressed . ^^^ Taken together these data indicate that the regulatory circuit involving Src and Csk PTKs was established prior to the divergence of the phylum Cnidaria from the rest of the metazoans . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
An inhibitor specific for Src family kinase or expression of Csk reduced tyrosine phosphorylation of nectin 2delta . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In this study , the role of this Arg ( Arg 318 ) in the protein tyrosine kinase C terminal Src kinase ( Csk ) was investigated . ^^^ Imidazole is the best of these activators , enhancing phosphorylation rates by Csk R318A up to 100 fold for poly ( Glu , Tyr ) and significantly stimulating Csk R318A phosphorylation of the physiologic substrate Src . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
C terminal Src kinase ( Csk ) has been demonstrated to negatively regulate Src family tyrosine kinases through tyrosine phosphorylation at the C terminal regulatory site ( Tyr 527 ) . ^^^ We report herein that down regulation of Src kinase activity by adenovirus mediated csk gene transfer abrogated the highly metastatic phenotype of colon cancer cells . ^^^ Overexpression of Csk decreased Src tyrosine kinase activity in NL 17 cells , the highly metastatic clone of mouse colon adenocarcinoma 26 . ^^^ These results provide a therapeutic basis for interfering with metastasis of colon cancer by csk gene mediated down regulation of Src kinase activity . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In reconstitution experiments , we first showed that expression in the RAW 264 . 7 cell line of C terminal Src kinase ( Csk ) inhibited and that of a membrane anchored , gain of function Csk abolished the Fc gamma R mediated signaling that leads to phagocytosis in a kinase dependent manner . ^^^ We next tested reconstruction of the signaling in the membrane anchored , gain of function Csk expressing cells by introducing Src family kinases the C terminal negative regulatory sequence of which was replaced with a c myc epitope . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Transmembrane phosphoprotein Cbp positively regulates the activity of the carboxyl terminal Src kinase , Csk . ^^^ Csk ( carboxyl terminal Src kinase ) is a cytoplasmic tyrosine kinase that phosphorylates a critical tyrosine residue in each of the Src family kinases ( SFKs ) to inhibit their activities . ^^^ The addition of the phosphorylated , but not nonphosphorylated , Cbp to an in vitro assay stimulated Csk activity toward Src . ^^^ Kinetic analysis revealed that Cbp or the phosphopeptide induced up to a 6 fold reduction in the K ( m ) for Src , indicating that the Csk . ^^^ Cbp complex has a greater affinity for Src than free Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition , negative regulators of these pathways , including CSK ( an inhibitor of SRC activity ) and PTP PEST ( a phosphatase that dephosphorylates p130Cas ) , bind directly to paxillin , thereby bringing them into close proximity with their targets . ^^^ Abbreviations : CAS , CRK associated substrate ; CH , calponin homology domain ; CSK , C terminal SRC kinase ; E 6 , Papillomavirus E 6 protein ; FAK , focal adhesion kinase ; GIT , GRK interacter ; GPCR , heterotrimeric G protein coupled receptor ; GRK , G protein coupled receptor kinase ; MAPK , mitogen activated protein kinase ( ERK , p 38 , JNK ) ; PAK , p 21 activated kinase ; PBS , paxillin binding subdomain ; PIX , PAK interacting exchange factor ; PKL , paxillin kinase linker ; POR 1 , partner of Rac ; PS , phosphoserine ; PT , phosphothreonine ; PY , phosphotyrosine ; RTK , growth factor receptor tyrosine kinase ; SH , SRC homology domain . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The protein tyrosine kinase ( PTK ) Csk is a potent negative regulator of several signal transduction processes , as a consequence of its exquisite ability to inactivate Src related PTKs . ^^^ This function requires not only the kinase domain of Csk , but also its Src homology 3 ( SH 3 ) and SH 2 regions . ^^^ In comparison , the Csk SH 2 domain interacts with several tyrosine phosphorylated molecules , presumed to allow targetting of Csk to sites of Src family kinase activation . ^^^ Transfection experiments indicated that Csk and PTP HSCF synergized to inhibit signal transduction by Src family kinases and that this cooperativity was dependent on the domains mediating their association . ^^^ Taken together , these results demonstrate that part of the function of the Csk SH 2 domain is to mediate an inducible association with a PTP , thereby engineering a more efficient inhibitory mechanism for Src related PTKs . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Activation of the COOH terminal Src kinase ( Csk ) by cAMP dependent protein kinase inhibits signaling through the T cell receptor . ^^^ Phosphorylation of residue Y 505 in Lck by COOH terminal Src kinase ( Csk ) , which negatively regulates Lck , is essential for the inhibitory effect of cAMP on zeta chain phosphorylation . ^^^ We propose a mechanism whereby PKA through activation of Csk intersects signaling by Src kinases and inhibits T cell activation . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We find that c Src , Lyn and Csk are enriched in the sphingolipid enriched fraction prepared from these cells . ^^^ We studied the association of Src family tyrosine kinases and their negative regulatory kinase , Csk , with sphingolipids in sphingolipid enriched domains of rat cerebellar granule cells differentiated in culture . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Release from tonic inhibition of T cell activation through transient displacement of C terminal Src kinase ( Csk ) from lipid rafts . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Third , it was appreciated that Csk , a potent inhibitor of Src kinases , is regulated by an assortment of protein protein interactions . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Our new findings demonstrate that Csk has no effect on ErbB 2 / neu activated Src kinases upon HRG treatment and that its kinase activity is not modulated by HRG . ^^^ These results indicate that CHK , but not Csk , is involved in HRG mediated signaling pathways , down regulates ErbB 2 / neu activated Src kinases , and inhibits invasion and transformation of breast cancer cells upon HRG stimulation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The cytoplasmic tyrosine kinase cSrc is involved in the regulation of many important cellular functions including cell growth and transformation , and its activity is down regulated by phosphorylation of the Tyr 530 residue by the COOH terminal Src tyrosine kinase , Csk . ^^^ We show that whereas no autoantibodies were found against cSrc or its relative Fyn , up to 20 % of patients with carcinoma had high affinity autoantibodies against Csk . ^^^ The COOH terminal Src kinase Csk is a tumor antigen in human carcinoma . ^^^ However a strong increase in Src activity was also observed in these tissues , which suggested that Csk can not regulate Src like activity in carcinoma . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
A relatively selective inhibitor of Src family kinases reduced cell cell adhesion dependent tyrosine phosphorylation of Gab 1 , whereas expression of a dominant negative mutant of Csk increased it . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Autonomous maturation of alpha / beta T lineage cells in the absence of COOH terminal Src kinase ( Csk ) . ^^^ The deletion of COOH terminal Src kinase ( Csk ) , a negative regulator of Src family protein tyrosine kinases ( PTKs ) , in immature thymocytes results in the development of alpha / beta T lineage cells in T cell receptor ( TCR ) beta deficient or recombination activating gene ( rag ) 1 deficient mice . ^^^ These data suggest a differential involvement of the Csk mediated regulation of Src family PTKs in positive and negative selection of developing thymocytes . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Molecular determinants for Csk catalyzed tyrosine phosphorylation of the Src tail . ^^^ The protein tyrosine kinase Csk is responsible for catalyzing the phosphorylation of this key Src tyrosine residue , but the detailed molecular basis for Src recognition and catalysis is poorly understood . ^^^ In this study , we investigate this phosphorylation event using purified recombinant Csk and Src proteins and mutants . ^^^ It was shown that the apparent k ( cat ) and K ( m ) values for Csk phosphorylation of catalytically impaired Src ( dSrc ) are similar to the parameters for Csk catalyzed phosphorylation of the Src family member Lck . ^^^ These results and other data suggest that Src dimerization ( or higher order oligomerization ) is important for high efficiency Csk catalyzed phosphorylation of the Src tail . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk ( C terminal Src kinase ) , a protein tyrosine kinase , consisting of the Src homology 2 and 3 ( SH 2 and SH 3 ) domains and a catalytic domain , phosphorylates the C terminal tail of Src family members , resulting in downregulation of the Src family kinase activity . ^^^ The Src family kinases share 37 % homology with Csk but , unlike Src family kinases , the catalytic domain of Csk alone is weakly active and can be stimulated in trans by interacting with the Csk SH 3 domain , suggesting a mode of intradomain regulation different from that of Src family kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Using a GST fusion protein carrying the cytoplasmic tail of beta dystroglycan , we identified five SH 2 domain containing proteins that interact with beta dystroglycan in a phosphorylation dependent manner , including c Src , Fyn , Csk , NCK , and SHC . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Transfection of the native Src inhibitor , C terminal Src kinase ( Csk ) , also suppressed crystal induced c Src , ERK1 / 2 , and IkappaBalpha phosphorylation and IL 8 expression . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The C terminal Src Kinase ( Csk ) is a potent inhibitor of Src activity , and is required for normal mammalian development ; here we report the characterization of Xenopus Csk ( Xcsk ) . ^^^ Xcsk activity requires a functional kinase domain ; furthermore , a kinase inactive Xcsk mutant potently synergizes with Laloo during early vertebrate development , suggesting a fundamental role for the Src kinase Csk regulatory circuit during mesoderm induction , in vivo . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Nucleotide release and associated conformational changes regulate function in the COOH terminal Src kinase , Csk . ^^^ The COOH terminal Src kinase ( Csk ) regulates a broad array of cellular processes via the specific phosphorylation and downregulation of Src family protein kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Protein tyrosine kinase Csk catalyzed phosphorylation of Src containing unnatural tyrosine analogues . ^^^ It appears that the tyrosine phenol hydroxyl is unlikely to be contributing significantly to Src ' s ground state binding affinity for Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Overexpression of Csk that inactivates Src family tyrosine kinases also inhibited ERK activation evoked by GH . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
C terminal Src kinase ( Csk ) takes part in a highly specific , high affinity interaction via its Src homology 3 ( SH 3 ) domain with the proline enriched tyrosine phosphatase PEP in hematopoietic cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Furthermore , the recent discovery that PKA regulates Src kinases through modulation of Csk , supports the notion that PKA is involved in the fine tuning of immune receptor signalling in lipid rafts . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Injection of mRNA coding for Csk , a natural inhibitor of Src kinase activity , produces the same phenotypic alterations . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Mek 1 activation by Gab1PH SHP2DeltaN was inhibited by an Src inhibitor and by Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Increased activity of c Src and Csk in fibroblasts transformed by 5 src oncogene . ^^^ In nontransformed cells , serum stimulation induced an enhanced Csk activity , but no changes in c Src activity were observed . ^^^ This may suggest that Csk may have more functions in hamster fibroblasts , in addition to its inhibitory effect on c Src . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We identified two proteins in this screen that interact with caveolin 1 in a phosphorylation dependent manner : tumor necrosis factor alpha receptor associated factor 2 ( TRAF 2 ) and C terminal Src kinase ( Csk ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To explore the overlapping functions of Src kinases , we have targeted Csk , a negative regulator of the Src family , to FA structures . ^^^ Expression of FA targeted Csk ( FA Csk ) effectively reduced the active form ( nonphosphorylated at the C terminal regulatory tyrosine ) of Src members in the cell . ^^^ Activated Src ( SrcY529F ) as well as activation of putative Src signaling mediators ( Fak , Cas , Crk / CrkL , C3G , and Rap 1 ) blocked the effect of FA Csk in a manner dependent on Rap 1 . ^^^ It is therefore likely that the primary cause of cell rounding and detachment induced by FA Csk involves dysfunction of FAs rather than caspase mediated apoptosis that may result from possible loss of survival signals mediated by Src family kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Further studies suggest that 5 Src phosphorylation sites on Dok 1 are critical for its binding to RasGAP and Csk , negative regulators of Src signaling . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Stretch induced activation of p 38 MAPK was abolished by overexpression of FAT and CSK , which are inhibitors of the FAK and Src families , respectively , and was suppressed by overexpression of a dominant negative mutant of Ras . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In conclusion , altered regulation of Ang 2 type 1 receptor activated c Src by Csk may be an important upstream modulator of abnormal ERK1 / 2 signaling in VSMCs from SHR . . ^^^ We investigated whether upregulation of Src by Ang 2 leads to increased extracellular signal regulated kinase 1 / 2 ( ERK1 / 2 ) phosphorylation in vascular smooth muscle cells ( VSMCs ) from spontaneously hypertensive rats ( SHR ) and whether these processes are associated with altered activation of C terminal Src kinase ( Csk ) , a negative regulator of Src . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Structure of the carboxyl terminal Src kinase , Csk . ^^^ The carboxyl terminal Src kinase ( Csk ) is an indispensable negative regulator for the Src family tyrosine kinases ( SFKs ) that play pivotal roles in various cell signalings . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Coordinate interactions of Csk , Src , and Syk kinases with [ alpha ] IIb [ beta ] 3 initiate integrin signaling to the cytoskeleton . ^^^ Csk , which negatively regulates Src by phosphorylating Tyr 529 , was also constitutively associated with alphaIIbbeta 3 . ^^^ However , fibrinogen binding caused Csk to dissociate from alphaIIbbeta 3 , concomitant with dephosphorylation of Src Tyr 529 and phosphorylation of Src activation loop Tyr 418 . ^^^ In contrast to the behavior of Src and Csk , Syk was associated with alphaIIbbeta 3 only after fibrinogen binding . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In contrast , the presence of micrometastases was strictly dependent on Src , since the percentage of mice bearing metastases was dramatically reduced by the expression of a dominant negative mutant of Src ( SrcK ) or of Csk , the natural inhibitor of Src . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In Y567F , Lyn activation on SCF stimulation decreased and C terminal Src kinase ( Csk ) suppressed KIT mediated Ca ( 2+ ) influx and cell migration , suggesting that Y 567 mediated Src family kinase ( SFK ) activation leads to Ca ( 2+ ) influx and migration . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Furthermore , cotransfection of wild type Lck with C terminal Src kinase ( Csk ) into JCaM1 . 6 failed to restore the chemotactic response induced by CXCL 12 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Furthermore , studies from our group indicate that the Csk homologous kinase ( CHK ) , a member of the Csk family , directly associates with HER2 / Neu and down regulates HER2 / Neu mediated Src kinase activation in breast cancer cells upon heregulin stimulation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Our previous studies demonstrated that Csk homologous kinase ( CHK ) acts as a negative growth regulator of human breast cancer through inhibition of ErbB 2 / neu mediated Src family kinase activity ( Bougeret , C . , Jiang , S . , Keydar , I . , and Avraham , H . ( 2001 ) J . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Mutation of csk , encoding the C terminal Src kinase , reduces Pseudomonas aeruginosa internalization by mammalian cells and enhances bacterial cytotoxicity . ^^^ Using fibroblasts homozygous for mutation of csk ( / ) , we tested the hypothesis that mutation of csk , encoding a negative regulator of Src family tyrosine kinases , would be important in P . aeruginosa invasion and cytotoxicity . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk is a soluble protein tyrosine kinase that phosphorylates and negatively regulates protein tyrosine kinases of the Src family . ^^^ Mutations that disrupted this coupling resulted in varying levels of decreases in Csk activity , and consistent and significant increases in K ( m ) values for its physiological substrate , Src protein tyrosine kinase . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To address this question we have investigated the effects of a series of both peptidic and non peptidic ligands of the SH 2 domain on Src kinase activation , both in vitro in an ELISA based assay and in vivo using csk and src double transformed Schizosaccharomyces pombe . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Constitutive exclusion of Csk from Hck positive membrane microdomains permits Src kinase dependent proliferation of Theileria transformed B lymphocytes . ^^^ Src family PTKs are known to be present in glycolipid enriched microdomains ( GEMs ) , also called lipid rafts , and to be negatively regulated by PTK Csk complexed to tyrosine phosphorylated transmembrane adapter protein PAG ( phosphoprotein associated with GEMs ) also called Cbp ( Csk binding protein ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Phosphorylation driven motions in the COOH terminal Src kinase , CSK , revealed through enhanced hydrogen deuterium exchange and mass spectrometry ( DXMS ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In the present study , we investigated the effect of overexpressing the Csk homologous kinase ( CHK ) , an inhibitor of Src family kinases , on the phosphorylation of Akt induced by two different factors : heregulin or cisplatin . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This series of compounds contained low nanomolar inhibitors of Src kinases with selectivity over Csk , epidermal growth factor receptor kinase , protein kinase C , and zeta associated 70 kDa protein . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Src inhibitor , PP 2 , the C terminal Src kinase ( Csk ) , and dominant negative Pyk 2 attenuated ERK1 / 2 activation by GnRH and PMA but not by EGF . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The phosphorylated CagA binds and activates SHP 2 phosphatase and thereby induces a growth factor like morphological change termed the `` hummingbird phenotype . ' ' In this work , we demonstrate that CagA is also capable of interacting with C terminal Src kinase ( Csk ) . ^^^ Upon complex formation , CagA stimulates Csk , which in turn inactivates the Src family of protein tyrosine kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We also show that Gab 2 phosphorylation is increased in Csk knockout cells in which Src family kinases are constitutively activated . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Proximal signalling pathways involve PTKs of the Src , Syk , Csk and Tec families , adapter proteins and effector enzymes in a highly organized tyrosine phosphorylation cascade . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Distinct roles of the Src family kinases , SRC 1 and KIN 22 , that are negatively regulated by CSK 1 in C . elegans . ^^^ To elucidate the primitive roles of the Src family kinases ( SFKs ) , here we characterized Caenorhabditis elegans orthologues of SFKs ( src 1 and kin 22 ) and their regulator kinase Csk ( csk 1 ) . ^^^ SRC 1 and KIN 22 possess the C terminal regulatory tyrosines characteristic of SFKs , and their activities are negatively regulated by CSK 1 in a yeast expression system . ^^^ The src 1 and csk 1 genes are co expressed in some head neurons , the anchor cell and the tail region , while kin 22 and csk 1 genes are co expressed in pharyngeal muscles and tail region . ^^^ These results suggest that SRC 1 and KIN 22 play distinct roles under the control of CSK 1 . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This correlated with decreased levels of raft localized Csk ( C terminal Src kinase ) kinase . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Activation of C terminal Src kinase ( Csk ) by phosphorylation at serine 364 depends on the Csk Src homology 3 domain . ^^^ In the present study , we investigate the mechanism for the protein kinase A ( PKA ) mediated activation of C terminal Src kinase ( Csk ) . ^^^ Although isolated Csk kinase domain was phosphorylated at Ser ( 364 ) by PKA to the same stoichiometry as wild type Csk , significant activation of the isolated Csk kinase domain by PKA was observed only in the presence of the purified Src homology 3 domain ( SH 3 domain ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Regulation of Src kinase activity is tightly coupled to the phosphorylation status of the C terminal regulatory tyrosine Tyr ( 527 ) , which , when phosphorylated by Csk , represses Src . ^^^ Here , we demonstrate that activation of Csk through a prostaglandin E ( 2 ) cAMP protein kinase A ( PKA ) pathway inhibits Src . ^^^ This inhibitory pathway is operative in detergent resistant membrane fractions where cAMP elevating agents activate Csk , resulting in a concomitant decrease in Src activity . ^^^ The inhibitory effect on Src depends on a detergent resistant membrane anchored Csk and co localization of all components of the inhibitory pathway in membrane microdomains . ^^^ Furthermore , epidermal growth factor induced activation of Src and phosphorylation of the Src substrates Cbl and focal adhesion kinase are inhibited by activation of the cAMP PKA Csk pathway . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In resting human T cells , PAG is tyrosine phosphorylated and associated with Csk , an inhibitor of Src related protein tyrosine kinases . ^^^ PAG mediated inhibition was accompanied by a repression of proximal TCR signaling and was rescued by expression of a constitutively activated Src related kinase , implying that it is due to an inactivation of Src kinases by PAG associated Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Transmembrane adapter proteins ( TRAPs ) are a relatively new and growing family of proteins that include linker for activation of T cells ( LAT ) , phosphoprotein associated with glycosphingolipid enriched micro domains ( PAG ) / C terminal Src kinase ( Csk ) binding protein ( Cbp ) , SHP 2 interacting transmembrane adapter protein ( SIT ) , T cell receptor interacting molecule ( TRIM ) , and the recently identified non T cell activation linker ( NTAL ) and pp 30 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk phosphorylates Src family tyrosine kinases and down regulates their activities in vitro and in vivo . ^^^ To gain insight into the integrin mediated cellular functions of this negative regulator of the Src family , we examined integrin mediated signals in Csk deficient fibroblasts ( Csk ( ) cells ) and their stable transfectants expressing re introduced Csk ( Csk ( ) / Csk cells ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
First , specific residues in Csk activation loop had little discernable functions in phosphorylation of its physiological substrate Src , as Ala scanning and loop replacement mutations decreased Csk activity toward Src less than 40 % . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The crystal structure of full length Csk ( C terminal Src kinase ) molecules shows a hydrophobic interaction between the SH 2 kinase linker residue Phe 183 and the alphaC helix of the catalytic domain . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Src family kinase inhibitor PP 2 and C terminal Src kinase ( Csk ) both alleviated HBx mediated PI 3 kinase activation and protection from TGF beta induced apoptosis . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Inhibition of the Src family kinases by either pharmacological inhibition using PP 2 or through a molecular approach by cell transfection with Csk was found to prevent the augmented LPS induced NF kappa B translocation caused by oxidants . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Interestingly , there was a concomitant increase in the phosphorylation of Fyn on its Csk ( C terminal Src kinase ) site , indicating feedback inhibition . ^^^ Our data suggest a novel mechanism for attenuation of Src kinase activity by Abl : stable tyrosine phosphorylation of a scaffolding protein , caveolin , and recruitment of Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In addition , tyrosine phosphorylated PSD 93 was able to bind to Csk , a negative regulator of Src family kinases , in vitro as well as in a brain lysate . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We speculate that the protein tyrosine kinase Csk ( C terminal Src kinase ) , which is also activated by Galphaq ( Q209L ) and Galphaq ( Q209L ) AA , acts upstream of GSK 3beta . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Overexpression of a dominant negative mutant of p130Cas ( CasDeltaSD ) , Crk ( CrkSH2m ) , Pyk 2 ( PKM ) , or C terminal Src kinase ( Csk ) , but not of a deletion mutant of EGFR ( 533delEGFR ) , attenuated ET induced JNK activation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CSK family contains two protein tyrosine kinases : Csk ( C terminal Src kinase ) and Chk ( Csk homologous kinase ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Supportively , inhibition of Src activity by overexpression of Csk resulted in attenuation of the tyrosine phosphorylation of VE cadherin and endothelial cell ( EC ) tube formation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Dual roles of the C terminal Src kinase ( Csk ) during developmental vascularization . ^^^ Here we report that C terminal Src kinase ( Csk ) , a tyrosine kinase that negatively regulates the activity of Src and related kinases , is important for vascular development . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Protein tyrosine kinases Src and Csk : a tail ' s tale . ^^^ Csk and Src are two protein tyrosine kinases with similar amino acid sequences but very different structures and functions . ^^^ Csk catalyzes a tail phosphorylation reaction on Src and thereby restrains Src ' s activity and oncogenic potential . ^^^ The molecular basis of the specificity of Csk targeting the Src tail appears to involve both local and long range interactions and illustrates the complexity of selective targeting in post translational modification . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Phospho LIME associates with the Src family kinase Lck and its negative regulator , Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Mechanism of Csk mediated down regulation of Src family tyrosine kinases in epidermal growth factor signaling . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CD 45 D2 bound similarly to Src family kinases but bound Csk to a lesser extent and did not bind significantly to the less related kinase , Erk 1 . ^^^ CD 45 dephosphorylated Lck and Src at similar rates but dephosphorylated Csk and Erk 1 at lower rates . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Cbp , a C terminal Src kinase ( Csk ) binding protein , is a transmembrane phosphoprotein that has been implicated in the regulation of the Src family kinase ( SFK ) through recruiting Csk , a negative regulator of SFK , to a membrane microdomain of lipid rafts . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
C terminal Src kinase ( Csk ) is a PTK that specifically phosphorylates Src family kinases on a C terminal Tyr . ^^^ Mutations in the docking site disabled Csk to phosphorylate , regulate , and complex with Src but only moderately affected its general kinase activity . ^^^ A peptide mimicking the docking site potently inhibited ( IC 50 = 21 microM ) Csk phosphorylation of Src but only moderately inhibited ( IC 50 = 422 microM ) its general kinase activity . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
SHP 2 dephosphorylated paxillin and caused dissociation of Csk , a negative regulator of Src , from paxillin but had no effect on paxillin Src association . ^^^ Together , these results reveal that Gab 1 recruits SHP 2 to dephosphorylate paxillin , leading to dissociation of Csk from the paxillin Src complex and Src activation and that Src is an SHP 2 effector involved in EGF stimulated Erk activation and cell migration . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Activation of Src kinase by overexpressing kinase dead Csk failed to reverse the inhibitory effect of Pyk 2 ( Y402F ) , suggesting that osteoclastic bone resorption requires both c Src kinase activity and the targeting of Src kinase by Pyk 2 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Shp 2 regulates SRC family kinase activity and Ras / Erk activation by controlling Csk recruitment . ^^^ Here , we show that Shp 2 promotes Src family kinase ( SFK ) activation by regulating the phosphorylation of the Csk regulator PAG / Cbp , thereby controlling Csk access to SFKs . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To establish whether the widely expressed regulator of Src family kinases Csk contributes to the control of acute inflammation in vivo , we inactivated csk in granulocytes by conditional mutagenesis ( Cre / loxP ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Oxidative stress activates both Src kinases and their negative regulator Csk and induces phosphorylation of two targeting proteins for Csk : caveolin 1 and paxillin . ^^^ Csk negatively regulates Src family kinases ( SFKs ) . ^^^ These data indicate that Csk may be more important for the return of Src kinases to the basal state than for the maintenance of basal activity in some cell types . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Although C terminal Src kinase ( CSK ) homologous kinase ( CHK ) is generally believed to inactivate Src family tyrosine kinases ( SFKs ) by phosphorylating their consensus C terminal regulatory tyrosine ( Tyr ( T ) ) , exactly how CHK inactivates SFKs is not fully understood . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Previously , we reported that Dok 3 is an inhibitor of B cell activation in A 20 B cells and that it associates with SHIP 1 , a 5 ' inositol specific lipid phosphatase , as well as Csk , a negative regulator of Src kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This study investigated the expression of molecules that regulate LCK homeostasis , such as CD 45 , C terminal Src kinase ( CSK ) , and c Cbl , in lipid raft domains from SLE T cells and investigated the localization of these proteins during T cell receptor ( TCR ) triggering . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Drosophila Src family kinases function with Csk to regulate cell proliferation and apoptosis . ^^^ Further , DCsk ( the Drosophila homolog of the C terminal Src kinase ) phosphorylates and interacts genetically with the wild type SFKs , but not with the constitutively active mutants in which a conserved C terminal tyrosine was mutated to phenylalanine , providing the first in vivo evidence that Csk regulates SFKs during development through phosphorylation of their C terminal tyrosine . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk , the physiological inhibitor of cSrc , was present in WI 38 but not in VA 13 GEM . ^^^ Both processes 1 and 2 were inhibited by GM 3 since they were enhanced by GM 3 depletion with d threo 1 phenyl 2 palmitoylamino 3 pyrrolidino 1 propanol ( P 4 ) . ( 3 ) The high level of inactive cSrc associated with growth inhibited cells was caused by coexisting Csk in WI 38 GEM . ( 4 ) Interaction of GM 3 with FGFR was demonstrated by binding of GM 3 to FGFR in the GEM fraction , as probed with GM 3 coated beads , and by confocal microscopy . ^^^ Continuous , constitutive activation of both cSrc and MAPK was due to ( 1 ) a much higher level of cSrc and FGFR in VA 13 than in WI 38 GEM , ( 2 ) their close association / interaction in VA 13 GEM as indicated by clear coimmunoprecipitation between cSrc and FGFR , and ( 3 ) the absence of Csk in VA 13 GEM , making GEM incapable of inhibiting cSrc activation . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This became apparent from the hyperresponsive degranulation of lyn / bone marrow derived mast cells , which is driven by hyperactivation of Fyn kinase that occurs , in part , through the loss of negative regulation by COOH terminal Src kinase ( Csk ) and the adaptor , Csk binding protein . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Expression of p 50 C terminal Src kinase ( Csk ) in mouse testis . ^^^ C terminal Src Kinase ( Csk ) is a cytoplasmic tyrosine kinase that phosphorylates a critical tyrosine residue in each of the Src family kinases to inhibit their activities . ^^^ To investigate the possible regulation of spermatogenesis by Src Csk loop , the postnatal changes in the expression of Csk were examined in mouse testes . ^^^ Src Csk loop may participate in the differentiation of the seminiferous epithelia and Leydig cells in mouse testis . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Multiple apoptotic signaling cascades are recruited by RAFTK as demonstrated by prevention of apoptosis using caspase 3 inhibitor 4 ( caspase 3 specific inhibitor ) , PP 2 ( Src specific kinase inhibitor ) , or Csk ( cellular negative regulator for Src ) , as well as dominant negative constructs for p38beta or MKP 1 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : Substantial evidence supports the suggestion that carboxyl terminal Src kinase ( Csk ) and Csk homologous kinase ( CHK ) , two negative regulatory kinases of the Src tyrosine kinase family , play distinct roles during development of the central nervous system ( CNS ) . ^^^ The authors observed an increase in CHK expression and a decline in Csk expression during differentiation of primary hippocampal neurons , but no difference in Src expression levels . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
To address this issue , an in vitro coculture system utilizing Sertoli and germ cells was used to study the regulation of several protein kinases , including c Src ( the cellular form of the 5 src transforming gene of Rous Sarcoma virus , RSV ) , carboxyl terminal Src kinase ( Csk ) , and casein kinase 2 ( CK 2 ) , during AJ assembly . ^^^ Both Sertoli and germ cells were shown to express c Src , Csk , and CK 2 with a relative Sertoli : germ cell ratio of approximately 1 : 1 , suggesting both cell types contributed equally to the pool of these kinases in the epithelium . c Src and Csk were shown to be stage specific proteins during the epithelial cycle , being highest at stages 7 8 . ^^^ An induction in c Src , Csk , and CK 2 were detected during Sertoli germ cell AJ assembly in vitro but not when Sertoli cells were cultured alone . ^^^ When adult rats were treated with 1 ( 2 , 4 dichlorobenzyl ) indazole 3 carbohydrazide ( AF 2364 ) , a compound known to induce germ cell loss from the seminiferous epithelium , in particular elongating / elongate and round spermatids , by disrupting Sertoli germ cell AJs , an induction of c Src and Csk , but not CK 2 , was detected . ^^^ This event was also associated with a loss of protein protein association of N cadherin and beta catenin from the cadherin / catenin / c Src / Csk / CK2 protein complex . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In manipulating Src family kinase ( SFK ) activity with knockdown of Csk or type 1 protein phosphatase ( PP 1 ) treatment , we observed coordinate increase and decrease in shear induced caveolin 1 phosphorylation , respectively . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In this system , the C terminal Src kinase ( Csk ) was shown to interact with CD85j . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We confirmed this result by showing that expression of two inhibitors of Src family function , dominant negative Src and CSK , also suppressed glioma cell invasion . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Dynamic coupling between the SH 2 domain and active site of the COOH terminal Src kinase , Csk . ^^^ The SH 2 domain is required for high catalytic activity in the COOH terminal Src kinase ( Csk ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
TGF beta 1 induction of such genes was significantly reduced in Src family tyrosine kinase deficient cells , and Csk and pharmacological inhibitors for Src family kinases or antioxidants inhibit the effects of TGF beta 1 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
One function of Lyp is downregulation of T cell signaling through its interaction with the negative regulatory kinase C terminal Src tyrosine kinase ( Csk ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
All members of the Src family of nonreceptor protein tyrosine kinases are phosphorylated and subsequently down regulated by the C terminal Src kinase , Csk . ^^^ To understand how Csk recognizes Src , the chemical / physical events that modulate apparent substrate affinity and turnover were investigated . ^^^ Taken together , the data are consistent with a mechanism whereby Csk achieves a low K ( m ) for the substrate Src , not by stabilizing protein protein interactions but rather by facilitating a fast phosphoryl transfer step . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
CD 45 also bound to phosphoprotein associated with glycosphingolipid enriched microdomains ( PAGs ) , which were subsequently dephosphorylated , resulting in the release of C terminal src kinase ( Csk ) from lipid rafts . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
C terminal Src kinase ( Csk ) contains a catalytic domain and a regulatory region , consisting of an SH 3 and an SH 2 domain . ^^^ First , kinetic characterization of SH 3 and SH 2 domain deletion mutants demonstrated that the SH 3 and SH 2 domains were crucial in maintaining the full activity of Csk , but were not directly involved in Csk recognition of its physiological substrate , Src . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The Csk tyrosine kinase negatively regulates the Src family kinases Lck and Fyn in T cells . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Modulation of TLR signalling by the C terminal Src kinase ( Csk ) in macrophages . ^^^ Among these proteins , we characterized C terminal Src kinase ( Csk ) , which negatively regulates Src like kinases in RAW 264 . 7 cells using RNAi knockdown technology . ^^^ The protein expression levels of a tyrosine kinase , Fgr , were reduced in Csk knockdown cells , suggesting that Csk is a critical regulator of TLR 4 mediated signalling by modifying the levels of Src like kinases . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Searching for proteins that could be involved in VE cadherin signaling , we found the cytosolic C terminal Src kinase ( Csk ) , a negative regulator of Src family kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The activity of all Src family kinases ( SFKs ) is controlled by phosphorylation at their C terminal 527 tyrosine residue by C terminal SRC kinase , CSK . ^^^ There is a paucity of information regarding the role of CSK and / or specific Src family kinases in neuronal differentiation . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Functional diversity of Csk , Chk , and Src SH 2 domains due to a single residue variation . ^^^ The C terminal Src kinase ( Csk ) family of protein tyrosine kinases contains two members : Csk and Csk homologous kinase ( Chk ) . ^^^ Recent reports suggest that the Src homology ( SH ) 2 domains of Csk and Chk may bind to different phosphoproteins , which provides a basis for different cellular functions for Csk and Chk . ^^^ To verify and characterize such a functional divergence , we compared the binding properties of the Csk , Chk , and Src SH 2 domains and investigated the structural basis for the functional divergence . ^^^ First , the study demonstrated striking functional differences between the Csk and Chk SH 2 domains and revealed functional similarities between the Chk and Src SH 2 domains . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Acute treatment with H ( 2 ) O ( 2 ) activated multiple signaling pathways , including the mitogen activated protein kinases ( MAPK ) members ( MAPK3 / 1 ERK2 / 1 , MAPK8 / 9 JNK1 / 2 , and MAPK 11 p38 ( mapk ) ) and the c src tyrosine kinase ( CSK ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Dok R mediates attenuation of epidermal growth factor dependent mitogen activated protein kinase and Akt activation through processive recruitment of c Src and Csk . ^^^ Herein , we have determined the structural determinants within Dok R that are required for its ability to attenuate EGF signaling and to associate with c Src and with the Src family kinase ( SFK ) inhibitory kinase , Csk . ^^^ We propose that recruitment of Csk to Dok R serves to bring Csk to c Src and down regulate its activity , resulting in a concomitant attenuation of MAPK and Akt / PKB activity . ^^^ Furthermore , we demonstrate that Dok R can abrogate c Src ' s ability to protect the breast cancer cell line SKBR 3 from anoikis and that an association with c Src and Csk is required for this activity . ^^^ Collectively these results demonstrate that Dok R acts as an EGFR recruited scaffolding molecule that processively assembles c Src and Csk to attenuate signaling from the EGFR . . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The initially described phosphorylation sites of Src include an activating phosphotyrosine 416 that results from autophosphorylation , and an inhibiting phosphotyrosine 527 that results from phosphorylation by C terminal Src kinase ( Csk ) and Csk homologous kinase . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Lyp is expressed in lymphocytes , where it physically associates through its proline rich motif ( called P 1 ) with the SH 3 domain of the protein tyrosine kinase Csk , an important suppressor of the Src family of kinases Lck and Fyn , which mediate TCR signaling . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
One is by modulating the interaction of alpha 3 with CD 9 ; the other is by activating or inhibiting the c Src activity , possibly through Csk translocation . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In resting platelets , c Src forms a complex with alphaIIbbeta 3 and Csk , which phosphorylates c Src tyrosine 529 to maintain c Src autoinhibition . ^^^ Fibrinogen binding to alphaIIbbeta 3 triggers PTP 1B recruitment to the alphaIIbbeta 3 c Src Csk complex in a manner that is dependent on c Src and specific tyrosine ( tyrosine 152 and 153 ) and proline ( proline 309 and 310 ) residues in PTP 1B . ^^^ Studies of PTP 1B deficient mouse platelets indicate that PTP 1B is required for fibrinogen dependent Csk dissociation from alphaIIbbeta 3 , dephosphorylation of c Src tyrosine 529 , and c Src activation . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The ubiquitously expressed transmembrane adaptor Csk binding protein ( Cbp ) recruits Csk to lipid rafts , where the latter exerts its negative regulatory effect on the Src family of protein tyrosine kinases . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
We report herein that prior to occurrence of neoplastic lesions in the azoxymethane rat model of colon carcinogenesis ; the tumor suppressor gene C terminal Src kinase ( Csk ) was down regulated with a concomitant increase in Src activity . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Coupled motions in the SH 2 and kinase domains of Csk control Src phosphorylation . ^^^ The C terminal Src kinase ( Csk ) phosphorylates and down regulates Src family tyrosine kinases . ^^^ To investigate this long range catalytic effect , the phosphorylation of Src and the conformation of Csk were investigated in the presence of a high affinity phosphopeptide derived from Cbp . ^^^ This peptide binds tightly to the SH 2 domain and enhances Src recognition ( lowers K ( m ) ) by increasing the apparent phosphoryl transfer rate in the Csk active site , a phenomenon detected in rapid quench flow experiments . ^^^ The binding of a small Cbp derived peptide to the SH 2 domain of Csk modifies these motions , enhancing Src recognition . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk homologous kinase ( CHK ) , unlike Csk , enhances MAPK activation via Ras mediated signaling in a Src independent manner . ^^^ Substantial evidence exists supporting the notion that Csk and CHK , two negative regulatory kinases of the Src tyrosine kinase family , play distinct roles during development of the nervous system . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The catalytic inhibitors include C terminal Src kinase ( CSK ) and CSK homologous kinase ( CHK ) that phosphorylate Y ( T ) of SFKs , as well as the protein tyrosine phosphatases that dephosphorylate pY ( A ) of the activated SFKs . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Using rapid mixing technologies , we demonstrate that the intrinsic thermodynamic affinities of two protein substrates for their respective kinases ( Csk with Src and Sky1p with Npl 3 ) are weak compared to their apparent affinities measured in traditional steady state kinetic assays ( i . e . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
C terminal Src kinase ( CSK ) and CSK homologous kinase ( CHK ) endogenous negative regulators of Src family protein kinases . ^^^ C terminal Src kinase ( CSK ) and CSK homologous kinase ( CHK ) are endogenous inhibitors of the Src family protein tyrosine kinases ( SFKs ) . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The activity of SFKs is inhibited by the presence of the carboxy terminal Src kinase ( Csk ) at the cell membrane . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Tyrosine phosphorylated CagA binds and activates SHP 2 phosphatase and the C terminal Src kinase ( Csk ) while inducing an elongated cell shape termed the `` hummingbird phenotype . ' ' Here we show that CagA reduces the level of focal adhesion kinase ( FAK ) tyrosine phosphorylation in gastric epithelial cells . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Using a yeast tri hybrid system , we found that phosphorylated LAIR 1 bound the C terminal Src kinase ( Csk ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The non receptor tyrosine kinase Src is inactivated by the C terminal Src kinase Csk . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Docking based substrate recognition by the catalytic domain of a protein tyrosine kinase , C terminal Src kinase ( Csk ) . ^^^ C terminal Src kinase ( Csk ) specifically phosphorylates Src family kinases on a C terminal Tyr residue , which down regulates their activities . ^^^ We have previously determined that Csk recognizes Src using a substrate docking site away from the active site . ^^^ In the current study , we identified the docking determinants in Src recognized by the Csk substrate docking site and demonstrated an interaction between the docking determinants of Src and the Csk substrate docking site for this recognition . ^^^ A similar mechanism was confirmed for Csk recognition of another Src family kinase , Yes . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The C terminal Src kinase ( Csk ) contains a catalytic domain and the regulatory SH 3 and SH 2 domains . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
TIMP 2 treatment of human microvascular endothelial cells ( hMVECs ) increased the phosphorylation levels of Src at Tyr 527 , the negative regulatory site , through enhanced association of Src with Csk . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
This peptide binds Src and inhibits its association with inhibitory kinase Csk , allowing autophosphorylation of Src at residue tyr 418 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Specifically , Dok 1 attenuates PDGF elicited c myc induction by recruiting Csk to active Src kinases , whereupon their activities and consequent c myc induction are diminished . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Tyrosine phosphorylated CagA specifically binds and deregulates SHP 2 via the Western CagA specific EPIYA C or East Asian CagA specific EPIYA D site , and C terminal Src kinase ( Csk ) via the EPIYA A or EPIYA B site . ^^^ Because Csk inhibits SFK , CagA with greater Csk binding activity more strongly inhibited Src dependent CagA phosphorylation and more effectively attenuated induction of cell elongation caused by CagA SHP 2 interaction . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk binding protein ( Cbp ) negatively regulates epidermal growth factor induced cell transformation by controlling Src activation . ^^^ Activation of Src is tightly regulated by the C terminal Src kinase ( Csk ) . ^^^ Its functions include suppression of T cell receptor activation through recruiting Csk and inhibiting Src family kinase ( SFK ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
PKA substrates involved in immune activation include transcription factors , members of the MAP kinase pathway , phospholipases and the Src kinase Csk . ^^^ The most proximal and major target for PKA phosphorylation is the C terminal Src kinase Csk which initiates a negative signal pathway that fine tunes the T cell activation process . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In this report , we showed that COOH terminal Src kinase ( CSK ) binds with and phosphorylates c Jun at Y 26 and Y 170 . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Role of SRC kinases in Neu induced tumorigenesis : challenging the paradigm using Csk homologous kinase transgenic mice . ^^^ To address whether Src activity is essential for Neu mediated tumorigenesis , we used a physiologic inhibitor of Src kinase activity , the Csk homologous kinase ( CHK ) , expressed as a mammary tissue specific transgene . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Characterization of the Src mutants confirmed that inactivation of Src by Csk through tail tyrosine phosphorylation required the Src SH 3 domain . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Csk differentially regulates Src 64 during distinct morphological events in Drosophila germ cells . ^^^ In this report , we demonstrate that regulation of Src 64 by Drosophila C terminal Src Kinase ( Csk ) contributes to the packaging of germline cysts by overlying somatic follicle cells during egg chamber formation . ^^^ These results uncover novel roles for both Csk and Src 64 in a dynamic event that involves adhesion , communication between cell types and control of cell motility . ^^^ Strikingly , Src 64 and Csk function in the germline to control packaging , not in migrating follicle cells , suggesting novel functions for this signaling cassette in regulating dynamic adhesion . ^^^ In contrast to the role played by Csk in the regulation of Src 64 activity during packaging , Csk is dispensable for ring canal growth control , indicating that distinct mechanisms control Src 64 activity during different morphological events . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Proteomics approaches permitted the identification of tyrosine kinases from three families : Src ( Lyn ) , Csk , and Tec ( Bmx , Btk ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The molecular machinery for cAMP dependent immunomodulation in T cells . cAMP inhibits Src family kinase signalling by PKA ( protein kinase A ) mediated phosphorylation and activation of Csk ( C terminal Src kinase ) . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
The switch is operated by the tyrosine kinase CSK , which itself is involved in a negative feedback loop with Src . ^^^ The model offers explanations for the existence of the positive and negative feedback loops involving protein tyrosine phosphatase alpha ( PTPalpha ) and translocation of CSK and predicts a specific relationship between Src phosphorylation and activity . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
Here , we show that the src gene family and its C terminal Src kinase ( Csk ) mediated regulatory system already were established in the unicellular M . ovata and that unicellular Src has unique features relative to multicellular Src : It can be phosphorylated by Csk at the negative regulatory site but still exhibits substantial activity even in the phosphorylated form . ^^^ When expressed in vertebrate fibroblasts , M . ovata Src can induce cell transformation irrespective of the presence of Csk . ^^^ These findings suggest that a structure of Src required for the stable Csk mediated negative regulation still is immature in the unicellular M . ovata and that the development of stable negative regulation of Src may correlate with the evolution of multicellularity in animals . . ^^^ |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
In contrast , overexpression of Csk inhibited tyrosine phosphorylation of cortactin and binding of cortactin to c Src . ^^^ |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P41240 and P12931 |
Pubmed |
SVM Score :0.0 |
NA |
|