Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.63717182
Site specific association of c Src with epidermal growth factor receptor in A 431 cells . 0.63717182^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.57687161
Growth potentiation was associated with the formation of a heterocomplex between c Src and activated EGFR , the appearance of a distinct tyrosyl phosphorylation on the receptor , and an enhancement of receptor substrate phosphorylation . 0.57687161^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.64983149
EGFR was found to associate with c Src in colon cancer cells and specific inhibitors of the EGFR resulted in a reduction of c Src activity to basal levels . 0.64983149^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.53031614
Potentiation correlated with the ability of c Src to physically associate with the activated EGFR and the appearance of two unique in vivo phosphorylations on the receptor ( Tyr 845 and Tyr 1101 ) . 0.53031614^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.66713342
Accumulating evidence indicates that interactions between the epidermal growth factor receptor ( EGFR ) and the nonreceptor tyrosine kinase c Src may contribute to an aggressive phenotype in multiple human tumors . 0.66713342^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.55088236
The epidermal growth factor receptor regulates interaction of the human DF3 / MUC1 carcinoma antigen with c Src and beta catenin . 0.55088236^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.54714273
Interestingly , activation of c Src and its association with transactivated EGFR is also observed in cells stimulated with non EGF agonists . 0.54714273^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.52172717
IGF 2 promoted direct association of c SRC with IGF IR , phosphorylated c SRC , and increased EGFR phosphorylation at tyrosine 845 , a c SRC dependent phosphorylation site . 0.52172717^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.5814876
The c Src tyrosine kinase associates with the catalytic domain of ErbB 2 : implications for ErbB 2 mediated signaling and transformation . c Src associates with and is activated by the ErbB 2 receptor tyrosine kinase , but is unable to bind the EGFR . 0.5814876^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :1.0321455
Endogenous pp60c src was found to tightly associate with tyrosine phosphorylated EGFR . 1.0321455^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :1.8090928
Furthermore , Csk inactivated Src was activated by interaction with Src phosphorylated EGF R but not by autophosphorylated EGF R . 1.8090928^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.58674752
Zn2+ induced the association of the EGFR with Src and specifically increased the phosphorylation of EGFR at tyrosine 845 ( Tyr 845 ) , a known Src phosphorylation site . 0.58674752^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.50667479
Src homology 2 containing tyrosine phosphatase ( SHP 2 ) was shown to be associated with EGFR during ET 1 treatment by EGFR coimmunoprecipitation . 0.50667479^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The purified fusion proteins ( GST TK 0 8 ) were tested as substrates for the tyrosine kinase activities of the EGFR and c src . ^^^ Both the GST TK 4 fusion protein , which contains the major C terminal tyrosine autophosphorylation sites of the EGFR , and GST TK 7 , which contains the connecting sequence between the EGFR kinase domain and the C terminal autophosphorylation domain , were strongly phosphorylated by the EGFR and c src . ^^^ 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: P12931 and P00533	Pubmed	SVM Score :0.0
To study the relationship between the tyrosine kinase c Src and the epidermal growth factor receptor ( EGF R ) , we used the breast cancer cell line ZR 75 1 , which was transfected with the EGF R . ^^^ 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 . . ^^^ Functional interaction between the epidermal growth factor receptor and c Src kinase activity . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
By contrast , the c Src SH 2 domain did not interact directly with tyrosine phosphorylated EGFR . ^^^ Moreover , in established cell lines expressing elevated levels of EGFR , EGF stimulation results in transphosphorylation of Neu and formation of complexes between c Src and tyrosine phosphorylated Neu . ^^^ Taken together , these observations suggest that activation of c Src by these two closely related EGFR family members results from a direct and specific interaction of c Src with tyrosine phosphorylated Neu . . ^^^ Direct and specific interaction of c Src with Neu is involved in signaling by the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We found no detectable transcripts of 9 proto oncogenes ( c sis , c met , c src , c lyn , c fgr , c ros , c pim , Blym and N myc ) , but detected transcripts of 12 other proto oncogenes ( int 2 , erbB , c abl , c raf 1 , c fyn , K ras , H ras , c mos , c myc , c myb , c fos , and c jun ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
However , purified EGFR did not phosphorylate recombinant PKC delta in vitro , whereas members of the Src family ( c Src , c Fyn ) and membrane preparations from keratinocytes did . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The phosphorylation of EGFR by c src was studied in order to evaluate the molecular basis for this interaction . ^^^ The C terminal autophosphorylation domain of EGFR was extensively phosphorylated by c src and EGFR kinase activities in vitro as determined by electrospay ionization mass spectrometry . ^^^ These studies revealed that Y 1086 was phosphorylated to a significantly higher extent by c src than by EGFR . ^^^ A subset of peptides corresponding to the eight possible tyrosine phosphorylation sites within the EGFR autophosphorylation domain was demonstrated to bind to the SH 2 domain of c src . ^^^ Finally , extensive c src phosphorylation of EGFR promoted its conversion to a form that exhibits high affinity ( KD = 380 nM ) and cooperative ( Hill coefficient ; n = 2 ) binding to the SH 2 domain of c src as measured by surface plasmon resonance . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
A role for epidermal growth factor receptor , c Src and focal adhesion kinase in an in vitro model for the progression of colon cancer . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Concomittantly , erbB 2 : EGFr heterodimer formation and c src kinase activity were also elevated in TPA treated epidermis . ^^^ In addition , activation of c src may be an important downstream effector in mouse keratinocytes both in vivo and in vitro , following activation of the EGFr , erbB 2 , or both . . ^^^ Activation of erbB 2 and c src in phorbol ester treated mouse epidermis : possible role in mouse skin tumor promotion . ^^^ 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: P12931 and P00533	Pubmed	SVM Score :0.0
Competitive inhibition of substrate binding and mutagenesis experiments with EGFR / Ufo constructs revealed C terminal tyrosine 821 ( EILpYVNMDEG ) as a docking site for multiple effectors , namely PLCgamma , p 85 proteins , GRB 2 , c src and lck . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
PD 089828 was found to inhibit human full length fibroblast growth factor ( FGF ) receptor 1 ( FGFR 1 ) , platelet derived growth factor ( PDGF ) receptor beta subunit ( PDGFR beta ) , Src nonreceptor tyrosine kinase ( c Src ) and epidermal growth factor ( EGF ) receptor ( EGFR ) tyrosine kinases with half maximal inhibitory potencies ( IC 50 values ) of 0 . 15 + / 0 . 02 ( n = 4 ) , 0 . 18 + / 0 . 04 ( n = 3 ) , 1 . 76 + / 0 . 28 ( n = 4 ) and 5 . 47 + / 0 . 78 ( n = 6 ) microM , respectively . ^^^ PD 089828 was further characterized as an ATP competitive inhibitor of the growth factor receptor tyrosine kinases ( FGFR 1 , PDGFR beta and EGFR ) but a noncompetitive inhibitor of c Src tyrosine kinase with respect to ATP . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Compound 4b inhibited the PDGFr , FGFr , EGFr , and c src tyrosine kinases with IC 50 values of 1 . 11 , 0 . 13 , 0 . 45 , and 0 . 22 microM , respectively . ^^^ Compound 4e inhibited the FGFr tyrosine kinase with an IC 50 of 0 . 060 microM , whereas IC50s for the inhibition of the PDGFr , FGFr , EGFr , c src , and InsR tyrosine kinases for this compound ( 4e ) were all greater than 50 microM . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
C Src is also overexpressed and / or activated in many of the same human carcinomas that overexpress members of the EGF receptor ( EGFR ) family , suggesting that the two types of tyrosine kinases can cooperate during the genesis of human tumors . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Previous studies have demonstrated a requirement for the nonreceptor tyrosine kinase , cellular Src ( c Src ) , in epidermal growth factor ( EGF ) induced mitogenesis and a synergistic interaction between c Src and EGF receptor ( EGFR ) in tumorigenesis . ^^^ Based on these reports , we examined EGFR trafficking behavior in a set of single and double c Src / EGFR C3H10T1 / 2 overexpressors to determine if c Src affects basal receptor half life , ligand induced internalization , and / or recycling . ^^^ Our results show that overexpression of c Src causes no change in EGFR half life but does produce an increase in the internalization rate constant of EGF . ^^^ EGFR complexes when the endocytic apparatus is not stoichiometrically saturated ; this effect of c Src on EGFR endocytosis is negligible at high receptor occupancy in cells overexpressing the receptor . ^^^ In neither case are EGFR recycling rate constants affected by c Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These results suggest that early upstream signaling events in response to heat stress may involve activation of PI 3 kinase and tyrosine kinases , such as c Src , and a growth factor receptor , such as EGFR ; activation of important downstream pathways , such as MAPK and p 70 S6K , occur by divergent signaling mechanisms similar to growth factor stimulation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Thrombin aivation of the 9E3 / CEF4 chemokine involves tyrosine kinases including c src and the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Characterization of human epidermal growth factor receptor and c Src interactions in human breast tumor cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
To understand the structural basis for the potency and specificity , a model for the binding mode of this class of inhibitors to the tyrosine kinase domains of c Src , PDGFr , FGFr , and EGFr tyrosine kinases was developed from structural information ( principally utilizing the catalytic domain of c AMP dependent protein kinase as template ) and structure activity relationship ( SAR ) information . ^^^
Interacting proteins: P12931 and P00533	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 ) . ^^^ 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 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In contrast , PD 166866 had no effect on c Src , platelet derived growth factor receptor beta , epidermal growth factor receptor or insulin receptor tyrosine kinases or on mitogen activated protein kinase , protein kinase C and CDK 4 at concentrations as high as 50 microM . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Compounds of this series were competitive with ATP and displayed submicromolar to low nanomolar potency against a panel of TKs , including receptor ( platelet derived growth factor , PDGFr ; fibroblast growth factor , FGFr ; epidermal growth factor , EGFr ) and nonreceptor ( c Src ) classes . ^^^ One of the more thoroughly evaluated members was 63 with IC 50 values of 0 . 079 microM ( PDGFr ) , 0 . 043 microM ( bFGFr ) , 0 . 044 microM ( EGFr ) , and 0 . 009 microM ( c Src ) . ^^^ In in vivo studies against a panel of seven xenograft tumor models with known and / or inferred dependence on the EGFr , PDGFr , and c Src TKs , compound 63 produced a tumor growth delay of 10 . 6 days against the relatively refractory SK OV 3 ovarian xenograft and also displayed activity against the HT 29 tumor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
One focus of investigation was epidermal growth factor receptor ( EGFR ) and the key cytosolic signaling kinases , c Src and protein tyrosine kinase ( PTK ) , whose responses to TCDD are well characterized . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Moreover , immunoblotting indicated that 14 , 15 EET stimulated tyrosine phosphorylation of the specific pp 60 ( c src ) substrate p 120 and c Src association with EGFR . 14 , 15 EET increased src kinase activity within 1 min . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The compound also inhibits signal transduction through fibroblast growth factor receptor 1 ( FGFR 1 ) , but is not active towards epidermal growth factor receptor ( EGFR ) or c Src tyrosine kinase . ^^^ Tyrosine kinase activity was modulated by inhibitors of beta PDGFR autophosphorylation in cells , but not by specific inhibitors of EGFR or c Src tyrosine kinase . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We have reported that angiotensin 2 ( Ang 2 ) induces Ca2+ dependent transactivation of the epidermal growth factor receptor ( EGFR ) which serves as a scaffold for preactivated c Src and downstream adaptors ( Shc / Grb2 ) , leading to ERK activation in cultured rat vascular smooth muscle cells ( VSMC ) . ^^^ Although a selective EGFR kinase inhibitor completely abolished Ang 2 induced recruitment of Grb 2 to EGFR and markedly attenuated Ang 2 induced ERK activation , it had no effect on Ang 2 induced PYK 2 tyrosine phosphorylation or its association with c Src and Grb 2 . ^^^ These data suggest that the AT 1 receptor uses Ca2+ dependent PYK 2 to activate c Src , thereby leading to EGFR transactivation , which preponderantly recruits Grb 2 in rat VSMC . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Starting with 5 S glutathionyl beta alanyl L dopa ( 1 ) and 5 S glutathionyl beta alanyl dopamine ( 2 ) , a series of analogues with truncated glutathionyl and beta alanyl dopa moieties were synthesized , and their inhibitory effects on autophosphorylation and substrate phosphorylation reaction by c Src and by epidermal growth factor receptor ( EGFR ) were evaluated . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In A 431 cells , Src is activated by the EGFR , and inhibition of the EGF receptor results in c Src inhibition . ^^^ The relative efficacies of the EGFR kinase inhibitor and of the Src kinase inhibitor are similar suggesting the major role src plays in the oncogenic signaling of EGFR in A 431 cells . ( 2 ) The Src kinase inhibitor PP 1 sensitizes A 431 cells to CDDP induced apoptosis . ( 3 ) CDDP induces caspase 3 dependent cleavage of the c Src C terminal portion and a concomitant reduction in Bcl 10 ( L ) levels . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
It is not active against kinases from other receptor families , such as epidermal growth factor receptor , fibroblast growth factor receptor 1 , c Met , and Tie 2 , or intracellular kinases such as c Src , c Abl , and protein kinase C alpha . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Although the mechanism of AT 1 ( or Ca2+ ) induced activation of EGFR is not yet clear , we have found that calcium dependent protein kinase CAKss / PYK2 and c Src are involved in this process . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
SP induced formation of an activated EGFR complex containing the adapter proteins SHC and Grb 2 , but not c Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Phosphopeptide maps of the EGFR phosphorylated in the presence of EGFR 13 or pp 60 ( c src ) demonstrated that the additional sites phosphorylated in the presence of EGFR 13 were the same as those phosphorylated by pp 60 ( c src ) ( i . e . , Y 803 , Y 845 , Y 891 , Y 920 , and Y 1101 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Upon EGF stimulation , c Src was rapidly recruited to Stat / ErbB receptor complexes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In this study we show that the induced expression of c SRC antisense RNA or the application of a selective Src kinase inhibitor induces growth arrest , programmed cell death and reverses the transformed properties of cells that overexpress EGFR or HER 2 receptors . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We extended these studies to cells overexpressing a receptor class tyrosine kinase , the epidermal growth factor ( EGF ) receptor ( EGFR cells ) ; like c Src , the EGF receptor is overexpressed in several human tumors . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
PD 166285 inhibited PDGFR beta , EGFR , and FGFR1TKs and c src TK by 50 % ( IC 50 ) at concentrations between 7 85 nM . ^^^
Interacting proteins: P12931 and P00533	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: P12931 and P00533	Pubmed	SVM Score :0.0
Indirect immunofluorescent study demonstrated that all Shc isoforms co localize with EGF receptor ( EGFR ) and activated c Src in both plasma membranes and cytoplasmic vesicle structures . ^^^ Our previous study has shown that EGF induces the indirect association of EGFR and c Src and activation of c Src in A 431 cells . ^^^ An immunoprecipitation study demonstrated that the EGFR Src association and c Src activation are augmented in cells expressing GFP Shc P 52 or P 66 , but not P 46 . ^^^ We also found that EGFR and Shc can be dissociated from c Src by the addition of a synthetic peptide that corresponds to the autophosphorylation site of c Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
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 . ^^^ Autophosphorylation of EGFr tyrosine kinase or PDGFr tyrosine kinase was not inhibited by c Src inhibitors , thus showing the selective nature of the compounds in cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Both of these reactive oxygen species serve as second messengers to activate multiple intracellular proteins and enzymes , including the epidermal growth factor receptor , c Src , p 38 mitogen activated protein kinase , Ras , and Akt / protein kinase B . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
It is not active against kinases from other receptor families such as EGFR , FGFR 1 , c Met and Tie 2 or intracellular kinases like c Src , c Abl , PKC alpha . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Tyrosine kinase signalling in breast cancer : epidermal growth factor receptor and c Src interactions in breast cancer . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Among 87 cases of HCC tested , 40 ( 46 % ) were positively stained for the activated c Src , and this positive staining was inversely correlated with the Ki 67 labeling index ( LI ) ( P = 0 . 0031 ) , intrahepatic metastasis ( P = 0 . 0099 ) , TNM stage ( P = 0 . 0062 ) , alpha fetoprotein ( P = 0 . 0103 ) and epidermal growth factor receptor expression ( P = 0 . 0153 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The early Ang 2 induced upstream signaling events responsible for transactivation of the EGF R , such as the intracellular Ca ( 2+ ) increase and c Src activation , also remain intact . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The EGFR phosphorylation by arsenic is ligand independent and does not involve the major autophosphorylation site Tyr ( 1173 ) . c Src activity is also induced by arsenic and is a prerequisite for the EGFR and ERK activation . ^^^ This response is also accompanied with an increase in c Src levels interacting with EGFR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We report here that elevated expression of PLD 2 transforms rat fibroblasts overexpressing either the EGFR or c Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Gbetagamma dependent activation of ERK requires tyrosine kinases , including epidermal growth factor receptor and c Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
By using a compound that selectively interferes with EGFR ( AG 1478 ) , c Src ( PP 1 ) , or disrupts actin cytoskeleton ( cytochalasin D ) , we demonstrated that cytochalasin D completely inhibited the activation of Pyk 2 , but not that of EGFR , whereas AG 1478 did not inhibit the activation of Pyk 2 , indicating that transactivation of EGFR and signaling pathways involving Pyk 2 were distinct pathways . ^^^ EGFR was Ca ( 2+ ) independently activated and predominantly contributed to Shc / ERK / c fos activation , while Pyk 2 or c Src contributed less to it . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Inhibition of matrix metalloproteinases ( MMPs ) , transforming growth factor alpha ( TGF alpha ) or c Src blocked PGE 2 mediated EGFR transactivation and downstream signaling indicating that PGE 2 induced EGFR transactivation involves signaling transduced via TGF alpha , an EGFR ligand , likely released by c Src activated MMP ( s ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Treatment of the cells with AG 1478 , a selective EGFR tyrosine kinase inhibitor , decreased Ang 2 mediated c Src phosphorylation , particularly in SHR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We show here that the Shc adaptor protein is a novel direct activator of c Src in epidermal growth factor receptor signaling in A 431 human epidermoid carcinoma cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
One of this pathways might include c Src dependent EGFR and MAPK activation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Furthermore , aldosterone enhanced Tyr phosphorylation of c Src and EGFR , and an inhibitor of cytosolic tyrosine kinases ( 4 amino 5 ( 4 chlorophenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyriociaine ) prevented the action of aldosterone . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Overexpression of the epidermal growth factor receptor ( EGFR ) and its association with the tyrosine kinase , c Src , is correlated with increased cellular proliferation and tumorigenesis . ^^^ Previous studies have shown that EGFR and c Src co overexpression and association leads to the c Src mediated phosphorylation of tyrosine 845 of the EGFR and that mutation of Tyr ( 845 ) ablates epidermal growth factor ( EGF ) induced DNA synthesis . ^^^ Here , we investigate the contribution of the signal transducers and activators of transcription ( STAT5b ) in the signaling pathways regulated by EGFR and c Src overexpression in human breast tumor cell lines as well as in a mouse fibroblast model ( C3H10T1 / 2 ) . ^^^ We demonstrate that 1 ) activation of STAT5b by EGF requires overexpression of the EGFR , 2 ) co overexpression of c Src alone does not result in EGF induced activation of STAT5b but enhances that seen in EGFR overexpressing cells , and 3 ) EGF induced tyrosine phosphorylation of STAT5b requires Tyr ( 845 ) of the EGFR . ^^^ Furthermore , the stable overexpression of a kinase defective c Src in the context of EGFR overexpression results in a decrease in the tyrosine phosphorylation of STAT5b in response to EGF and a more dramatic decrease in EGF induced transcriptional activation of STAT5b , suggesting an integral role for c Src in the physiological actions of STAT5b . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
CDDP induces the activation of c Src , and EGFR activation is blocked by Src family inhibitor PP 1 , suggesting that Src kinases mediate CDDP induced EGFR activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We hypothesized that the GLP 1R could activate PI 3 kinase and promote beta cell proliferation through transactivation of the epidermal growth factor ( EGF ) receptor ( EGFR ) , an event possibly linked to GPCRs via activation of c Src and the production of putative endogenous EGF like ligands . ^^^ Both the c Src inhibitor PP 1 and the EGFR specific inhibitor AG 1478 blocked GLP 1 induced [ ( 3 ) H ] thymidine incorporation in INS ( 832 / 13 ) cells as well as in isolated rat islets , while only AG 1478 inhibited the proliferative action of betacellulin ( BTC ) , an EGFR agonist . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Our study addressed the mode of oncogenic cooperation and reports that overexpression of c Src in model cellular systems results in the accumulation of EGFR at the cell surface . ^^^ In conclusion , by promoting destruction of c Cbl , c Src enables EGFR to evade desensitization , which explains Src EGFR collaboration in oncogenesis . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Internalization of EGFR by these ligands involves the tyrosine kinase activity of the receptor itself and c Src , as well as the GTPase activity of dynamin . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
CONCLUSIONS : Because most breast carcinomas overexpress c Src , it behooves one to question the extent to which reducing the amount of EGF and consequent EGFR activity will decrease invasion . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The EGFR and a number of effector kinases ( mitogen activated protein extracellular signal regulated kinase kinase 1 and 2 , MAPK , Pak 1 , p 38 , c JunNH ( 2 ) terminal kinase and extracellular signal regulated kinase 1 ) and cell survival proteins ( AKT , FKHR , and c Src ) showed constitutive pathway activation in HaCaT and cutaneous squamous cell carcinoma cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Therefore , in the rat pituitary , the increase of pERK is a Gq and PLC dependent process , which involves an increase in intracellular calcium and activation of a c Src tyrosine kinase , transactivation of the EGFR , and the activation of MEK . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Co immunoprecipitation analysis demonstrated interaction between c Src and STATs 3 or 5 and EGFR in SCCHN cells , but no heterodimerization was detected between STAT 3 and STAT 5 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Plasma membrane phospholipid scramblase 1 promotes EGF dependent activation of c Src through the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	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 . ^^^ In summary , Zn ( 2+ ) ions induce EGFR phosphorylation in a manner dependent on c Src but not on EGFR dimerization or EGFR kinase activation , suggesting that Zn ( 2+ ) induces EGFR transactivation by c Src . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Bromocriptine caused protein kinase B ( Akt ) activation in PC 12 D2R cells and the inhibition of either phosphoinositide ( PI ) 3 kinase , epidermal growth factor receptor ( EGFR ) , or c Src eliminated the Akt activation and the cytoprotective effects of bromocriptine against oxidative stress . ^^^ Co immunoprecipitation studies showed that the D 2 receptor forms a complex with the EGFR and c Src that was augmented by bromocriptine , suggesting a cross talk between these proteins in mediating the activation of Akt . ^^^ D 2 receptor stimulation by bromocriptine induced c Src tyrosine 418 phosphorylation and EGFR phosphorylation specifically at tyrosine 845 , a known substrate of Src kinase . ^^^ Thus , the predominant signaling cascade mediating cytoprotection by the D 2 receptor involves c Src / EGFR transactivation by D 2 receptor , activating PI 3 kinase and Akt . ^^^ These results support the hypothesis that specific dopamine agonists stabilize distinct conformations of the D 2 receptor that differ in their coupling to G proteins and to a cytoprotective c Src / EGFR mediated PI 3 kinase / Akt pathway . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) and c Src phosphorylation levels together with protein expression of 5 LOX were also significantly enhanced in this proliferation process . ^^^ Inhibitors of EGFR and c Src alleviated the actions of nicotine on cell proliferation and 5 LOX protein expression . ^^^ In contrast , 5 LOX inhibitor had no direct effect on the phosphorylation levels of EGFR and c Src and yet inhibited cell proliferation . ^^^ Inhibitors of EGFR , c Src , and 5 LOX all significantly impeded the tumor growth induced by nicotine . ^^^ Activation of the phosphorylated form of EGFR and c Src followed by an increased 5 LOX expression are the prime pathogenic mechanisms in the tumorigenic process in the colon . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Cell surface receptor for the epidermal growth factor ( EGFR ) and cytoplasmic tyrosine kinase c Src co operate in several cellular functions such as proliferation and apoptosis . ^^^ Co incubation of purified c Src and EGFR results in phosphorylation of Tyr 845 in vitro , indicating that c Src can directly phosphorylate EGFR on Tyr 845 . ^^^ CONCLUSION : These results indicate that multiple signals for c Src activation can promote Stat 3 / 5 phosphorylations through Src dependent phosphorylation of EGFR on Tyr 845 . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In addition , ZD 1839 suppressed EGF induced stimulation of EGFR autophosphorylation on Y 1086 and Grb 2 binding Y 1068 sites , c Src phosphorylation on Y 215 , and Pak 1 activity . ^^^ CONCLUSIONS : These studies suggest that the EGFR TKI ZD 1839 may cause potent inhibition of the Pak 1 and c Src pathways and , therefore , have potential to affect the invasiveness of human cancer cells deregulated in these growth factor receptor pathways . . ^^^ The epidermal growth factor receptor tyrosine kinase inhibitor ZD 1839 ( Iressa ) suppresses c Src and Pak 1 pathways and invasiveness of human cancer cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We also determined that cisplatin induced ERK as well as caspase 3 activation are epidermal growth factor receptor ( EGFR ) and c src dependent because inhibition of these genes inhibited ERK and caspase 3 activation and attenuated apoptotic death . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Numerous studies have demonstrated an interaction between MUC 1 and other oncogenic proteins such as beta catenin , erbB receptors and c Src , but a functional role for MUC 1 in transformation has not been identified . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
When co overexpressed , the epidermal growth factor receptor ( EGFR ) and c Src cooperate to cause synergistic increases in EGF induced DNA synthesis , soft agar colony growth , and tumor formation in nude mice . ^^^ This synergy is dependent upon c Src mediated phosphorylation of a unique tyrosine on the EGFR , namely , tyrosine 845 ( Y 845 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Tumors exhibited increased association of Egfr with clathrin heavy chain ( CHC ) , Gab 1 , and p85alpha , the regulatory subunit of phosphoinositide 3 kinase ( PI3K ) , and tumors also overexpressed c Src , PDK 1 , and Akt . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Indeed , in DU 145 cells , GnRH a activates the JNK cascade in a c Src and MLK 3 dependent manner but does not involve protein kinase C and epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We find that neither MAPK 1 / 2 nor c Src is signaling intermediaries between EGFR and ENaC . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
However , STATs can also be activated by growth factor receptors , particularly the EGFR ; as well as by members of the Src Family of Kinases ( SFKs ) , particularly c Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The additional molecular targets considered here include the type 1 insulin like growth factor receptor , the epidermal growth factor receptor , mammalian target of rapamycin , NF kappaB , hypoxia inducible factor 1alpha , hsp 90 , cyclooxygenase 2 , protein kinase A type 1 , vascular endothelial growth factor , 5 lipoxygenase , 12 lipoxygenase , angiotensin 2 receptor type 1 , bradykinin receptor type 1 , c Src , interleukin 6 , ras , MDM 2 , bcl 2 / bclxL , vitamin D receptor , estrogen receptor beta , and PPAR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Because TCDD leads to phosphorylation of the epidermal growth factor receptor and an increase in c Src activation in WB F 344 cells , we investigated the functional relevance of this observation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Src family kinase inhibitors block amphiregulin mediated autocrine ErbB signaling in normal human keratinocytes . c Src potentiates proliferation , survival , and invasiveness in response to epidermal growth factor ( EGF ) in human mammary carcinoma cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Furthermore , gene silencing with PKCdelta small interfering RNA ( siRNA ) , siRNA against c Src , and mutant c Src ( S12C / S48A ) and treatment with a c Src inhibitor ( 4 amino 5 ( 4 chlorophenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyrimidine ) abrogated PMA induced EGFR phosphorylation at Tyr ( 1068 ) . ^^^ Taken together , our data demonstrate that PMA transactivates the EGFR and increases cell proliferation by activating the PKCdelta / c Src pathway in glioblastomas . . ^^^ Phorbol 12 myristate 13 acetate induces epidermal growth factor receptor transactivation via protein kinase Cdelta / c Src pathways in glioblastoma cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These data indicate that two major phenotypic characteristics of TGF beta 1 exposure ( i . e . , transcription of specific target genes [ e . g . , PAI 1 ] , increased cell motility ) are linked in the R 22 vascular smooth muscle cell system , require pp 60 ( c src ) kinase activity and MEK signaling and involve activation of an AG 1478 sensitive ( likely EGFR dependent ) pathway . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In addition , the phosphorylation of Y 845 on EGFR by EGF , which is mediated through c Src or related kinases but not autophosphorylation , was also affected by MNNG . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
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: P12931 and P00533	Pubmed	SVM Score :0.0
Treatment of CCLP 1 cells with PGE 2 or ONO DI 004 enhanced binding of EGFR to the EP 1 receptor and c Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We show that TGF beta 1 activates the epidermal growth factor receptor ( EGFR ) and phosphorylates c Src . ^^^ The activation of c Src by TGF beta 1 is EGFR dependent and is required for full Akt phosphorylation and cell survival . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) and the non receptor tyrosine kinase c Src phosphorylate CaM ( Y99F ) and CaM ( Y138F ) at a lesser extent than wild type CaM , while they fail to phosphorylate CaM ( Y99F / Y138F ) as expected . ^^^ Quantitative analysis of the different phospho ( Y ) CaM species suggests that the relative phosphorylation of Y 99 and Y 138 in wild type CaM by both the EGFR and c Src is different than the respective phosphorylation of either Y 99 in CaM ( Y138F ) or Y 138 in CaM ( Y99F ) . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In addition , we provide evidence for cytoplasmic tyrosine kinase ( c Src ) involvement in the SDF 1 / CXCR4 EGFR transactivation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Low concentration of ouabain also induced endocytosis of the Na / K ATPase and compartmentalization of some signaling molecules ( e . g . c Src , EGFR , and p42 / 44 MAPKs ) into clathrin coated pits , early and late endosomes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Therapeutic maneuvers may target receptor tyrosine kinases ( EGFR , VEGFR , FGFR ) , chemokines or G protein coupled receptors ( CXCR 4 , CXCR 2 , EphB 2 ) , hypoxia inducible factor ( HIF ) , and signaling pathways ( c Src , PI3K , Akt , chaperon complexes ) in tumor cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Biochemical studies revealed that TKI 28 potently inhibited the activities of tyrosine kinases such as ErbB 2 , EGFR , KDR , PDGFRbeta , c kit and c Src , but had little effect on Flt 1 in cell free system . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These effects of PGF2alpha on the FP receptor could be abolished by treatment of cells with a specific FP receptor antagonist , chemical inhibitors of c Src , matrix metalloproteinase , and EGFR kinase or by inactivation of signaling with dominant negative mutant isoforms of EGFR , Ras , or MEK or with small inhibitory RNA oligonucleotides targeted against the EGFR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In concert with these results , we show that heregulin ( HRG ) , a ligand for ErbB receptors , activates c Src and , in turn , stimulates binding of MUC 1 to HSP 90 . ^^^ These findings indicate that MUC 1 is delivered to mitochondria by a mechanism involving activation of the ErbB receptor > c Src pathway and transport by the molecular chaperone HSP70 / HSP90 complex . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The EP ( 1 ) induced EGFR transactivation and cell invasion involves c Src , in light of the presence of native binding complex of EP ( 1 ) / Src / EGFR and the inhibition of PGE ( 2 ) induced EGFR phosphorylation and cell invasion by the Src siRNA and the Src inhibitor , PP 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Using dominant negative mutants of c Src and Fyn and Src deficient SYF cells as well as by co immunoprecipitation studies , we can demonstrate that the M2R mediated transactivation of EGFR specifically involves Fyn but not c Src or Yes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In order to elucidate the mechanism of Zn2+ induced EGFR activation in HAEC , we treated HAEC with 500 microM ZnSO 4 for 5 20 min and measured the state of activation of EGFR , c Src and PTPs . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
For example , prostaglandin E ( 2 ) ( PGE ( 2 ) ) induced transactivation of the EGF receptor ( EGFR ) in colorectal carcinoma cells is mediated by means of a c Src dependent mechanism and regulates cell proliferation and migration . ^^^ Here we report that PGE ( 2 ) induces the association of a prostaglandin E receptor 4 / beta arrestin 1 / c Src signaling complex resulting in the transactivation of the EGFR and downstream Akt ( PKB ) signaling . ^^^ These results show that the prostaglandin E / beta arrestin 1 / c Src signaling complex is a crucial step in PGE ( 2 ) mediated transactivation of the EGFR and may play a pivotal role in tumor metastasis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Maximal immediate early PAI 1 induction upon exposure to TGF beta 1 required EGFR , p21ras , MEK and pp 60 ( c src ) signaling as pharmacologic or dominant negative inhibition of any of the four intermediates ( EGFR , p21ras , MEK , pp 60 ( c src ) ) virtually eliminated TGF beta 1 augmented PAI 1 levels . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In vascular smooth muscle cells ( VSMCs ) , through its G protein coupled AngII Type 1 receptor ( AT ( 1 ) ) , AngII activates various intracellular protein kinases , such as receptor or non receptor tyrosine kinases , which includes epidermal growth factor receptor ( EGFR ) , platelet derived growth factor receptor ( PDGFR ) , c Src , PYK 2 , FAK , JAK 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This EGFR supported transactivation is strongly dependent on EGFR tyrosine kinase , c Src , and the c Src specific EGFR tyrosine residue 845 and represents a novel paradigm of EGFR transactivation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The interaction between the SH 2 domain of c Src and the phosphorylated EGFR C terminal domain was shown to impede its mobility . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The role of c Src in mediating angiotensin 2 and arachidonic acid signaling was determined by employing immunocomplex kinase assay , Western blotting analysis , and protein immunoblotting on co precipitated EGF receptor ( EGFR ) proteins and agarose conjugates of glutathione S transferase fusion proteins containing the c Src homology 2 ( SH 2 ) and SH 3 domains . ^^^ Angiotensin 2 induced extracellular signal regulated kinase ( ERK ) activation in primary cultures of rabbit proximal tubule cells via the activation of c Src and association of the EGFR with the c Src SH 2 domain , effects that were mimicked by arachidonic acid and its inactive analogue eicosatetraynoic acid . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
MCF 7 cells overexpressing Cas exhibited increased phosphorylation of two c Src substrates , Tyr 845 in the kinase domain of the epidermal growth factor receptor ( EGFR ) and signal transducer and activator of transcription ( STAT ) 5b . ^^^ Based on these findings , we suggest that the Cas / c Src / EGFR / STAT5 signaling axis is a major regulator of tamoxifen resistant breast cancer cell growth and survival . . ^^^ Physical and functional interactions between Cas and c Src induce tamoxifen resistance of breast cancer cells through pathways involving epidermal growth factor receptor and signal transducer and activator of transcription 5b . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In addition , p 60 Src or Lyn kinase phosphorylated recombinant RGS 16 in vitro , and RGS 16 underwent phosphorylation in the presence of constitutively active Src ( Y529F ) in EGFR ( ) CHO K 1 cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Solid phase ELISAs for the determination of EGF receptor ( EGF R ) and pp60c src tyrosine protein kinase activity are described . ^^^ The methods were developed and optimized using purified recombinant EGF R intracellular domain ( ICD ) and pp60c src tyrosine protein kinases . ^^^ Development of solid phase enzyme linked immunosorbent assays for the determination of epidermal growth factor receptor and pp60c src tyrosine protein kinase activity . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Substrate specificity and kinetic characterization of src family tyrosine kinases including human platelet pp60c src , bovine p56lyn , p56lck , and p55fyn , as well as several non src related tyrosine kinases including epidermal growth factor receptor , p43v abl , TK 3 , and TK 4 showed that all the src family tyrosine kinases but none of the other kinases displayed efficient cdc 2 ( 6 20 ) NH 2 phosphorylation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
One of these isolated products was at least 10 fold more inhibitory to both pp60c src and epidermal growth factor receptor kinase activity than the parent tyrphostin . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In mononuclear cytotrophoblasts , pp60c src was localized at cell matrix contacts and during the aggregation of cytotrophoblasts , pp60c src was distributed on the cell surface at points of cell cell contact being colocalized with EGF R and E cadherin . ^^^ Inhibition of pp60c src by herbimycin A at 0 . 25 to 1 microgram / ml during the first day of culture was associated with a decreased expression of tyrosine kinase activity of EGF R and an increase in E cadherin expression . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Whilst radiation induced pp60c Src activity was not modulated due to BBI pre treatment , activation of epidermal growth factor receptor ( EGFR ) was inhibited . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Our results suggest that activated macrophages have a tumor progressive effect on HepG 2 cells which involves the c Src and EGFR dependent signaling cascades . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In parallel , activation of COX 2 / PGE ( 2 ) signaling also enhances Stat 3 phosphorylation and reporter activity through EP ( 1 ) receptor induced activation of c Src and EGFR in these cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These tests were negative except for erbB which showed faint hybridization with the genome of ASV 25 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
After transfection with human MR , aldosterone induced a rapid and dose dependent phosphorylation of ERK1 / 2 and c Jun NH 2 terminal kinase ( JNK ) 1 / 2 kinases in Chinese hamster ovary or human embryonic kidney cells , which was reduced by the MR antagonist spironolactone and involved cSrc kinase as well as the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Ang 2 induced EGF R transactivation is mediated through cSrc , a proximal target of reactive oxygen species ( ROS ) derived from NAD ( P ) H oxidase ( NOX ) and is dependent on AT ( 1 ) R trafficking through caveolin 1 ( Cav 1 ) enriched lipid rafts . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Presence of SH 2 domains of phospholipase C gamma 1 enhances substrate phosphorylation by increasing the affinity toward the epidermal growth factor receptor . src homology region 2 and 3 ( SH 2 and SH 3 ) domains are conserved noncatalytic regions originally described in cytoplasmic tyrosine kinases and subsequently identified in phospholipase C gamma 1 ( PLC gamma 1 ) , GTPase activating protein of ras , and other signaling proteins . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Direct analysis of the binding of Src homology 2 domains of phospholipase C to the activated epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This subpopulation of 5 Src may have been recovered from the plasma membrane via the endocytotic pathway in a manner analogous to endocytosis of the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
High efficiency expression / cloning of epidermal growth factor receptor binding proteins with Src homology 2 domains . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This phosphatase specifically dephosphorylates phosphotyrosine containing substrates , including the src peptide , the epidermal growth factor receptor tyrosine kinase and the non receptor tyrosine kinase p56lck . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This compound did not significantly inhibit the tyrosine protein kinase activity of the epidermal growth factor receptor and was found to be a less effective tyrosine protein kinase inhibitor for other members of the src family of protein kinases . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
However , transcriptional activation of a proto oncogene like erbB , ras , raf , src , and c myc , which are all involved in the progression pathway of EGF , may be a common feature of NSCLC . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
CNE 323 transferred moderate transforming activity when introduced into JB 6 P+ cells and showed no homology to Ha , Ki , or N ras genes ; human promotion sensitivity genes ; src , myb , jun , myc , fos , raf , or int 2 oncogenes ; or epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The p56lck protein is a member of the src family and its homology with receptor kinases such as the epidermal growth factor receptor ( EGFR ) make it an important candidate in signal transduction . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We also measured the steady state level of second messengers in 32D cells transformed by erbB , abl , and src oncogenes which abrogate growth factor requirement . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Frequently multiple oncogenes were found expressed although expression levels were rather moderate . 25 30 % of the analyzed tumors showed significant expression of either erbB , src , raf 1 , lck or H ras . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Inhibition of epidermal growth factor receptor biosynthesis caused by the src oncogene product , pp60v src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Many oncogenes including src , ras , sis , fms and erbB are known to activate cellular phosphatidylinositol ( PI ) turnover . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Transformation of chicken embryo fibroblasts ( CEF ) with viruses encoding src , ros , yes , and fps as well as ras , mos , middle T , erbA and erbB , myc , and crk stimulated 9E3 mRNA expression . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Subsequently it was found that this line could be transformed neoplastically by a variety of retrovirus containing H ras , bas , fes , fms , erbB , and src oncogenes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Transformation of chicken embryo fibroblasts by direct DNA transfection of single oncogenes : comparative analyses of src , erbB , myc , and ras . ^^^ Transfection of src , myc , erbB , and ras , either singly or in combination , resulted in soft agar colonies with unique morphologies . ^^^ This method should prove useful in analyzing oncogenes , ( e . g . , myc ) that do not readily transform rodent cell lines and in studying host range mutants of oncogenes , such as those recently identified for src and erbB . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
No expression of the proto oncogenes src , myb , myc , ros , mos , erbA , and erbB was detected . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Probes utilized represent 11 known oncogenes ( erbB 1 , gli , neu , myc , L myc , N myc , H ras , K ras , N ras , sis , and src ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The analysis includes the oncogenes myc , sis , mos , erbB , erbA , Ha ras , Ki ras , src , fps , and abl . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
RNA isolated from involved skin of psoriatic patients was subjected to dot blot hybridization with cloned viral Ki ras , myc , abl , fos , src , erbB , mos , sis , fes , and yes oncogenes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
It was found that the antibiotic was effective against the cells transformed by tyrosine kinase oncogenes src , yes , fps , ros , abl , erbB , but did not reverse the transformed morphologies induced by oncogenes raf , ras , and myc . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Northern blot analysis was performed with eight oncogene probes ( myc , fos , Ha ras , src , erbA , erbB , sis , myb ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Extensive analysis of a pool of 15 cellular protooncogenes ( Ha ras , Ki ras , N ras , mos , fos , fes , myc , abl , sis , myb , erbA , erbB , src , raf , N myc ) , using Southern and northern blot analysis , was done to determine whether mutagen induced rearrangement , amplification or overexpression of any of these genes was responsible for the mutagen induced , anchorage independent phenotype . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We report here that transfection of the oncogenes 5 src , erbB , c myc , 5 myc , N myc , and EJras into these cells does not result in detectable PA activity in conditioned media or cell extracts . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Similar to other tyrosine kinase oncogenes ( erbB , src , fps , sea ) , the 5 fms oncogene induced progenitor cells to self renew in an erythropoietin independent manner . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Subsequently , it was found that this line could be transformed neoplastically by a variety of retroviruses containing H ras , bas , fes , fms , erbB and src oncogenes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
A transient three to four fold increase in erbB proto oncogene expression and a similar although smaller increase in src expression was observed during the period of time when events committing the cells to differentiate were occurring , but prior to the expression of the differentiated phenotype . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In the present study , nontumorigenic human epidermal keratinocytes , immortalized by Ad 12 SV40 virus or pSv 3 neo , were transformed by a variety of retroviruses containing bas , H ras , fes , fms , erbB and src oncogenes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
There are sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
A member of the SRC gene family , the c erbB 1 gene , is closely related to the EGF receptor gene ] . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The sequence of the erbB gene is furthermore related to that of other viral transforming genes such as src , fps , yes or abl . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Sis and N ras were moderately hyperexpressed , raf , Blym , and erbA were slightly hyperexpressed , and abl , erbB , fes / fps , fgr , fos , mos , myb , myc , N myc , rasHarvey , rasKirsten , ros , src , and yes were not hyperexpressed in the tumor compared to the control tissue . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
For src , ras , erb B and sis a differential expression during embryogenesis and / or in normal organs was detected , with preferential expression of src in neural tissues , a high abundance of sis transcripts in an embryonal epitheloid cell line and of erbB transcripts in the head nephros . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Association with expression of abl , ras , fes , src , erbB , and Cas NS 1 oncogenes but not with myc . ^^^ This antigen was expressed on many pre B and B cell lymphomas , but not on A MuLV transformed fibroblasts , T cell lymphomas , or myelomonocytic leukemias , gp 160 ( 6C3 ) was expressed by most early B lineage spontaneous tumors , and early B tumors induced by replication defective MuLV containing oncogenes the products of which are associated with the cytoplasmic aspect of the plasma membrane , i . e . , fes , abl , H ras , bas , src , erbB , and Cas NS 1 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The complementary DNA sequence of the human insulin receptor is similar to those of the EGF receptor ( erbB oncogene ) and products of the src family of oncogenes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This gene shares structural and sequence homologies with the epidermal growth factor receptor ( erb B oncogene ) and members of the src family of oncogenes , suggesting that alterations in the insulin receptor , resulting from chromosomal translocation , could lead to a role in tumorigenesis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The mil protein shares homology with a number of onc proteins such as src , fes , fms , mos , yes , fps and erbB , as well as with the catalytic chain of the cAMP dependent protein kinase . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These results demonstrate that several members of the src gene family other than erbB have the capacity to transform erythroid cells . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The erbB gene of avian erythroblastosis virus is a member of the src gene family . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The erbB oncogene , which is homologous to a portion of the epidermal growth factor receptor , is related to the src family of oncogenes and efficiently transforms erythroblasts , whereas erbA potentiates the effects of erbB by blocking the differentiation of erythroblasts at an immature stage . ^^^ A src related oncogene such as erbB in synergy with an activated specific cell derived gene such as erbA can profoundly affect early erythroid differentiation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The data suggest that the substrate specificity of the insulin activable protein kinase is similar to that reported for the src and epidermal growth factor receptor protein kinases . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Previous studies indicated that Tyr 457 of bovine GAP ( Tyr 460 of human GAP ) is the major site of phosphorylation by viral Src ( 5 Src ) kinase and epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This assay measures inhibition of binding of a fusion construct ( glutathione S transferase src SH 3 SH2 ) with autophosphorylated epidermal growth factor receptor tyrosine kinase domain . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Together with Src protein , other oncogene products including Yes , Fps , ErbB and Crk were also found to stimulate the secretion of metalloproteinases . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Structural requirements of the epidermal growth factor receptor for tyrosine phosphorylation of eps 8 and eps 15 , substrates lacking Src SH 2 homology domains . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Direct analysis of the binding of the abl Src homology 2 domain to the activated epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Disease specificity of kinase domains : the src encoded catalytic domain converts erbB into a sarcoma oncogene . src and erbB are two tyrosine kinase encoding oncogenes carried by retroviruses , which have distinct disease specificities . ^^^ Src and ErbB have similar catalytic domains but have very different regulatory domains . ^^^ Here we show that the Src catalytic domain is enzymatically active when substituted into the ErbB backbone and interacts with the ErbB regulatory domain . ^^^ This ErbB / Src chimera displays autophosphorylation and substrate phosphorylation patterns different from those of both Src and ErbB . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Transcripts coding for transcription factors ( RB , P 53 , FOS , MYC , MYB , ERBA , REL ) , growth factors ( FGF 1 , FGF 2 , INT 2 , TGFA , TGFB , PDGF , IGF 1 , IGF 2 ) , interleukins , ( IL 1 , IL 2 , IL 3 , IL 4 , IL 6 , TNF ) , growth factor receptors or cytosolic protein kinases ( RAF , PIM , FES , MET , SRC , ROS , TRK , KIT , CSFR , IGFR , PDGFR , EGFR , NEU ) were quantified in cultured human mammary fibroblasts from normal tissues , benign tumours , carcinomas and post radiation fibrosis lesions by slot blot autoradiography and image analysis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Activated epidermal growth factor receptor ( EGFR ) undergoes autophosphorylation on several cytoplasmic tyrosine residues , which may then associate with the src homology 2 ( SH 2 ) domains of effector proteins such as phospholipase C gamma 1 ( PLC gamma 1 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
However , the expression of other genes such as epidermal growth factor receptor , glial fibrillary acidic protein , and several proto oncogenes ( src , fos and myc ) , and a cholinergic marker such as choline acetyltransferase activity were unaltered . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NIH3T3 transformants from a tertiary round of transfection were analysed by Southern blot analysis for the presence of Ki ras , N ras , raf , trk , abl , fms , src , mos , fos , sis , fps , erbA , erbB or neu oncogenes of REC origin , and none were detected . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NIH / 3T3 cells transformed by the activated oncogenes erbB , src , and raf , showed increased levels of GSH with concomitant alterations in the levels of GSH related enzymes . ^^^ Transfection and over expression of a synthetic gene coding for a phosphotyrosine protein phosphatase ( PTPase ) , which inhibited the proliferation of normal and transformed NIH / 3T3 cells , was accompanied by a decrease in GSH levels in normal and erbB transformed fibroblasts , and by an increase in src and raf transformants . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Here , we observed tyrosine phosphorylation of C cbl in cells expressing epidermal growth factor receptor depending on EGF stimulation and in 5 src transformed cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In this study , platelet derived growth factor receptor phosphorylation of Src on Tyr 213 specifically blocked binding of its SH 2 domain to a phosphopeptide corresponding to the C terminal regulatory sequence , while binding to other sequences , such as the platelet derived growth factor receptor or a peptide from the epidermal growth factor receptor , was unaffected . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Here we have evaluated 21 gliomas for amplification of tumor related genes including NMYC , EGFR , TGFalpha , MET , CMYC , SRC , HRAS , NRAS , SEC , ROS 1 , JUN , and WNT 1 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
METHODS : Immunodetection was used to compare the expression and tyrosine phosphorylation state of PLC gamma 1 , EGFR , phosphatidylinositol 3 kinase ( PI 3 kinase ) , ras guanosine triphosphatase activating protein ( GAP ) , and src homologous collagen like protein ( SHC ) in the postnatal rat intestine . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We have utilized a transient cotransfection model system in epidermal growth factor ( EGF ) responsive cultured GH 4 rat pituitary neuroendocrine cells to investigate the role of Ras in coupling EGF receptor ( EGF R ) and 5 Src tyrosine kinase signals to the activation of a cell specific promoter for the rat ( r ) prolactin ( PRL ) gene . ^^^ Ras mediates Src but not epidermal growth factor receptor tyrosine kinase signaling pathways in GH 4 neuroendocrine cells . p21Ras has been implicated as a critical signaling component in mediating the effects of many growth factor receptor / tyrosine kinases on cell growth and differentiation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We measured glutathione ( GSH ) metabolism in normal NIH / 3T3 fibroblasts , and in cells transformed by the oncogenes sis , erbB , src , ras , dbl , and raf . erbB , src , ras and raf , but not sis and dbl transformants , showed increased level of total and reduced GSH as compared with normal NIH / 3T3 fibroblasts ; oxidized GSH was elevated only in src and ras transformed cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Sequence specificity in the recognition of the epidermal growth factor receptor by the abl Src homology 2 domain . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The two glioblastomas with multiple chromosomal changes showed increased EGFr , Ki ras , myb , mos and myc , decreased H ras and N ras and unchanged levels of abl , src and sis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The exchange of nerve growth factor receptor / Trk and epidermal growth factor receptor ( EGFR ) phospholipase C gamma ( PLC gamma ) binding sites resulted in the transfer of their distinct affinities for this Src homology 2 domain containing protein . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Epidermal Growth Factor Receptor ( EGF R ) becomes constitutively tyrosine phosphorylated on two novel sites in 5 Src transformed cells , and these phosphorylations are associated with enhanced signaling activity [ 1 ] . ^^^ The ability of Src to phosphorylate the EGF R is consistent with the suggestion that the receptor can function as a kinase substrate independent of its intrinsic enzymatic activity , as implied by recent studies on signaling by kinase defective EGF Rs . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
To deduce the role of these residues in tyrosine kinase function , site directed mutations were prepared in the epidermal growth factor receptor ( EGFR ) and in 5 Src and effects on ATP binding and kinase activity were determined . ^^^ Changing the orientation of this sequence impaired activity of EGFR to a greater extent than that of 5 Src but did not change substrate specificity of the two enzymes . ^^^ Analysis of sequence inversions in the catalytic loop indicate that the active site of 5 Src exhibits greater flexibility than that of EGFR . . ^^^ Mutational analysis of the nucleotide binding site of the epidermal growth factor receptor and 5 Src protein tyrosine kinases . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Candidate protein tyrosine kinases that link G protein coupled receptors with MAP kinase include Src family kinases , the epidermal growth factor receptor , Lyn and Syk . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Gbetagamma subunits mediate Src dependent phosphorylation of the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In the nontransformed intestinal cell line IEC 6 , expression of EGFR , Src homology and collagen protein ( SHC ) , phospholipase C gamma 1 ( PLC gamma ) , and their tyrosine phosphorylation in response to EGF was assayed by immunoblot . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
However , TGFalpha protein was not secreted by RIE 1 cells stably expressing 5 Src or activated Raf , and only minor increases in EGFR ligand mRNA expression were detected in these cells . ^^^ A selective EGFR tyrosine kinase inhibitor PD 153035 attenuated the Ras , but not Src , transformed phenotype . ^^^ Finally , we suggest that an EGFR dependent mechanism is necessary for Ras , but not Src , transformation of these intestinal epithelial cells . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Incubation of supB+ cells with ( 13S ) HPODE and EGF increased EGFR autophosphorylation and tyrosine phosphorylation on several signaling proteins with Src homology 2 domains including GTPase activating protein . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
After binding to EGFR , PTP1B becomes tyrosine phosphorylated at Tyr 66 , a site that conforms to the consensus binding sequence for the Src homology 2 ( SH 2 ) domains of the adapter protein Grb 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This review covers the literature on significant studies of small molecule inhibitors of the epidermal growth factor receptor ( EGFR ) , platelet derived growth factor receptor ( PDGFR ) , fibroblast growth factor receptor ( FGFR ) , Flk 1 , and src family tyrosine kinases from 1996 through mid 1997 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Balanol does not , however , inhibit the Src or epidermal growth factor receptor protein tyrosine kinases . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Furthermore , the Src tyrosine kinase inhibitor PP 1 strongly interfered with LPA and EGF induced tyrosine phosphorylation and MAPK activation downstream of EGFR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
PD 166285 was found to inhibit Src nonreceptor tyrosine kinase , fibroblast growth factor receptor 1 , epidermal growth factor receptor and platelet derived growth factor receptor beta subunit ( PDGFR beta ) , tyrosine kinases with half maximal inhibitory potencies ( IC 50 values ) of 8 . 4 + / 2 . 3 nM ( n = 6 ) , 39 . 3 + / 2 . 8 nM ( n = 16 ) , 87 . 5 + / 13 . 7 nM ( n = 6 ) and 98 . 3 + / 7 . 9 nM ( n = 16 ) , respectively . ^^^ PD 166285 was further characterized as an ATP competitive inhibitor of Src nonreceptor tyrosine kinase , PDGFR beta , fibroblast growth factor receptor 1 and epidermal growth factor receptor tyrosine kinases . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Grb 10 interacts differentially with the insulin receptor , insulin like growth factor 1 receptor , and epidermal growth factor receptor via the Grb 10 Src homology 2 ( SH 2 ) domain and a second novel domain located between the pleckstrin homology and SH 2 domains . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The increase in GCF 2 , like the decrease in the epidermal growth factor receptor mRNA , is not seen in PC12nnr5 cells nor in cells expressing either dominant negative Ras or dominant negative Src . ^^^ The results suggest that nerve growth factor induced down regulation of the epidermal growth factor receptor is under transcriptional control , is p 140 ( trk ) , Ras , and Src dependent , and may involve transcriptional repression by GCF2 . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Mutation in the Src homology ( SH ) 2 or amino terminal SH 3 domain did not abolish the binding of CrkII 23 to EGFR in the quiescent cells , suggesting that the binding is mediated by a novel mechanism . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Two broad specificity biotinylated PTK peptide substrates were identified with optimum kinetic properties , allowing members from eight distinct classes of enzymes , including transmembrane ( epidermal growth factor receptor ( EGFR ) , fibroblast growth factor receptor , insulin receptor , and platelet derived growth factor receptor ) and cytoplasmic ( p 43 ( abl ) , p 56 ( lck ) , p 60 ( src ) , and p 93 ( fes ) ) PTKs , to be analyzed . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The src homology 2 and phosphotyrosine binding domains of the ShcC adaptor protein function as inhibitors of mitogenic signaling by the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
EAST , an epidermal growth factor receptor and Eps 15 associated protein with Src homology 3 and tyrosine based activation motif domains . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
ErbB 2 binding to peptides containing the Src homology 2 domain of Grb 2 or p 85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
To investigate early signaling mechanisms used by the EGFR in prostate tumor cells , we have characterized the involvement of the Shc ( src homology 2 / x collagen related ) adapter protein in EGFR signaling in several human prostate tumor cell lines . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Activation of the Src family of kinases or of the Ras / MAPK pathway can , however , be initiated by a kinase impaired EGFR and is linked to survival . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
EGF mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of SRC kinase by EGF receptor ( EGFR ) signaling . ^^^ These observations demonstrate a role for SRC kinase in modification and recruitment of clathrin during ligand induced EGFR endocytosis and thereby define a novel effector mechanism for regulation of endocytosis by receptor signaling . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Tumor suppressor genes ( p 53 , p 16 ) , oncogenes ( c erbB 2 , H ras , K ras , cyclin D 1 , src ) , and growth factor / receptor ( TGF alpha , EGFR ) seem to cause the malignant transformation of Barrett ' s esophagus . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
By using both genetic and biochemical approaches , we have investigated the physiological role of Shp 2 , a cytoplasmic tyrosine phosphatase with two Src homology 2 domains , in signaling pathways downstream of epidermal growth factor receptor ( EGF R ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In vitro , Tub is phosphorylated by purified insulin receptor kinase as well as by Abl and JAK 2 but not by epidermal growth factor receptor and Src kinases . ^^^
Interacting proteins: P12931 and P00533	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 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The two SH 2 ( Src homology domain 2 ) domains present in phospholipase C gamma 1 ( PLC gamma 1 ) were assayed for their capacities to recognize the five autophosphorylation sites in the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
AP 1510 treatment induced tyrosine phosphorylation of ErbB 1 and ErbB 2 homodimers and recruitment of Src homology 2 domain containing proteins ( Shc and Grb 2 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Tyrosine kinases such as src localize to the adherens junctions and phosphorylate junctional proteins in both normal and transformed cells . ( 1 ) p 120 ( ctn ) forms a complex with E cadherin at the adherens junction and is phosphorylated by ligands such as epidermal growth factor receptor as well as pp 60 src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In vitro phosphorylation assays showed that PDGF receptor , calcium dependent tyrosine kinase ( CADTK / Pyk 2 ) , Src kinase , and epidermal growth factor receptor all were able to phosphorylate purified annexin 7 and 11 on tyrosine residues . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Many tyrosine kinases , such as the epidermal growth factor receptor , Her 2 / Neu , Src , and Axl , are known to play a role in oncogenic signals in transformed cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
EGFR , HER 3 , c myc and SRC were not expressed . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Coincident with EGFR transactivation , isoproterenol exposure induces the formation of a multireceptor complex containing both the beta ( 2 ) AR and the `` transactivated ' ' EGFR . beta ( 2 ) AR mediated EGFR phosphorylation and subsequent beta ( 2 ) AR stimulation of extracellular signal regulated kinase ( ERK ) 1 / 2 are sensitive to selective inhibitors of both EGFR and Src kinases , indicating that both kinases are required for EGFR transactivation . beta ( 2 ) AR dependent signaling to ERK1 / 2 , like direct EGF stimulation of ERK1 / 2 activity , is sensitive to inhibitors of clathrin mediated endocytosis , suggesting that signaling downstream of both the EGF activated and the GPCR transactivated EGFRs requires a productive engagement of the complex with the cellular endocytic machinery . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Most notably , G ( q / 11 ) induced ERK activation was sensitive to N 17 Ras and to expression of the C terminal Src kinase but also to other dominant negative mutants of signaling components localized upstream of Ras , like Shc and the EGFR . ^^^ GnRH as well as phorbol esters led to Ras activation in COS 7 and alphaT 3 1 cells , which was dependent on Src and EGFR tyrosine kinases , indicating that both tyrosine kinases act downstream of protein kinase C ( PKC ) and upstream of Ras . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
CCh also induced tyrosine phosphorylation of p 60 ( src ) and association of p 60 ( src ) with both PYK 2 and the EGFR . ^^^ The Src family kinase inhibitor , PP 2 ( 20 nM 20 microM ) attenuated CCh stimulated EGFR and ERK phosphorylation and potentiated chloride secretory responses to CCh . ^^^ We conclude that CCh stimulated transactivation of the EGFR is mediated by a pathway involving elevations in intracellular Ca ( 2+ ) , calmodulin , PYK 2 , and p 60 ( src ) . ^^^ Carbachol stimulated transactivation of epidermal growth factor receptor and mitogen activated protein kinase in T ( 84 ) cells is mediated by intracellular ca ( 2+ ) , PYK 2 , and p 60 ( src ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
EGFR , PDGFR ) or cytoplasmic ( Src , Abl ) tyrosine kinases are found mutated in a variety of human tumors . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Involvement of Src and epidermal growth factor receptor in the signal transducing function of Na+ / K+ ATPase . ^^^ In both cell types , ouabain stimulated Src kinase activity , Src translocation to the Triton insoluble fraction , Src association with the epidermal growth factor receptor , and the tyrosine phosphorylation of this receptor on site ( s ) other than its major autophosphorylation site , Tyr ( 1173 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These compounds were evaluated for their inhibitory properties toward VEGF R 2 ( Flk 1 / KDR ) , FGF R 1 , PDGF Rbeta , p 60 ( c ) ( ) ( ) ( ) ( Src ) ( ) , and EGF R tyrosine kinases and their ability to inhibit growth factor dependent cell proliferation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Interestingly , NGF down regulated the expression levels of WT 1 and EGFR in PC 12 cells , but not in the p 140 ( trk ) deficient variant PC12nnr5 cells or in cells expressing either dominant negative Ras or dominant negative Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The interaction of activated epidermal growth factor receptor ( EGFR ) with the Src homology 2 ( SH 2 ) domain of the growth factor receptor binding protein Grb 2 initiates signaling through Ras and mitogen activated protein kinase ( MAP kinase ) [ 1 , 2 ] . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The activation of Pak 1 by wounding is blocked by inhibitors of phosphatidylinositol 3 kinase , and Src family kinases , but not by an inhibitor of the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In this study , activation of the Gq / G11 coupled thromboxane A 2 ( TxA 2 ) receptor ( TP ) by the TxA 2 mimetic IBOP in ECV 304 cells was found to induce extracellular regulated kinase ( ERK ) phosphorylation and tyrosine phosphorylation of the epidermal growth factor receptor ( EGFR ) , which were inhibited by the TP antagonist SQ 29548 , the EGFR kinase inhibitor AG 1478 , the Src family kinase inhibitor PP 1 , the Gi / o protein inhibitor pertussis toxin ( PTX ) , or the protein kinase C ( PKC ) inhibitor calphostin C . ^^^ TP activation also increased Src kinase activity , which was blocked by PTX , PP 1 , and calphostin C , but not by AG 1478 , indicating that Src activation occurs before phosphorylation of EGFR . ^^^ In conclusion , TPalpha is directly coupled to the Gi protein by a PKC regulated mechanism ; Gi coupling causes Src dependent transactivation of the EGFR , which is the dominant pathway in TP mediated ERK activation . . ^^^ The thromboxane A 2 receptor activates mitogen activated protein kinase via protein kinase C dependent Gi coupling and Src dependent phosphorylation of the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Src tyrosine kinase inhibitor PP 2 ( 4 amino 5 ( 4 chlorophenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyrimidine ) and the epidermal growth factor receptor tyrosine kinase inhibitor AG 1478 ( 4 ( 3 chloroanilino ) 6 , 7 dimethoxyquinazoline ) also had no effect on adenosine A ( 1 ) receptor stimulation of p42 / p44 MAPK . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Src and Pyk 2 mediate G protein coupled receptor activation of epidermal growth factor receptor ( EGFR ) but are not required for coupling to the mitogen activated protein ( MAP ) kinase signaling cascade . ^^^ The epidermal growth factor receptor ( EGFR ) and the non receptor protein tyrosine kinases Src and Pyk 2 have been implicated in linking a variety of G protein coupled receptors ( GPCR ) to the mitogen activated protein ( MAP ) kinase signaling cascade . ^^^ In this report we apply a genetic strategy using cells isolated from Src , Pyk 2 , or EGFR deficient mice to explore the roles played by these protein tyrosine kinases in GPCR induced activation of EGFR , Pyk 2 , and MAP kinase . ^^^ We show that Src kinases are critical for activation of Pyk 2 in response to GPCR stimulation and that Pyk 2 and Src are essential for GPCR induced tyrosine phosphorylation of EGFR . ^^^ By contrast , Pyk 2 , Src , and EGFR are dispensable for GPCR induced activation of MAP kinase . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Consistent with this observation , H ( 2 ) O ( 2 ) stimulated EGFR tyrosine phosphorylation and complex formation with Shc Grb 2 that was abolished by PP 2 , implicating Src in H ( 2 ) O ( 2 ) induced EGFR activation . ^^^ These data indicate that H ( 2 ) O ( 2 ) induced JNK activation in endothelial cells involves the EGFR through an Src dependent pathway that is distinct from EGFR ligand activation . ^^^ Jun N terminal kinase activation by hydrogen peroxide in endothelial cells involves SRC dependent epidermal growth factor receptor transactivation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In addition to BCR / ABL , STI 571 also inhibits 5 Abl , TEL / ABL , the native platelet derived growth factor ( PDGF ) beta receptor , and c KIT , but it does not inhibit SRC family kinases , c FMS , FLT 3 , the epidermal growth factor receptor , or multiple other tyrosine kinases . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Experiments with various chemical inhibitors and dominant inhibitory mutants demonstrate that EGFR dependent activation of the ERK cascade after alpha ( 2A ) AR stimulation requires Gbetagamma subunits upstream and dynamin dependent endocytosis downstream of HB EGF shedding and EGFR activation , whereas Src kinase activity is required both for the release of HB EGF and for HB EGF mediated ERK 2 phosphorylation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Its activity is strongest on cyclin dependent kinases ( cdk 1 , 2 , 4 , 6 , 7 ) and less on receptor tyrosine kinases ( EGFR ) , receptor associates tyrosine kinases ( pp 60 Src ) and on signal transducing kinases ( PKC and Erk 1 ) . ^^^ Moreover , direct and indirect inhibition of receptor activation ( EGFR ) and / or a direct inhibition of kinases ( pp 60 Src , PKC , Erk 1 ) involved in the signal transduction pathway could play a role in the antiproliferative activity of flavopiridol . ^^^ However , no in situ data from flavopiridol treated cells have been published yet that prove that by inhibition of EGFR , pp 60 Src , PKC and / or Erk 1 ( in addition to inhibition of cdk ' s ) flavopiridol is able to induce apoptosis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Src homology 2 domain of SHIP 2 was unable to precipitate the EGFR in EGF stimulated cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Phosphorylation could be blocked by pharmacological inhibitors of Src family tyrosine kinases or the epidermal growth factor receptor tyrosine kinase , but not by inhibitors of the platelet derived growth factor receptor or phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Furthermore , inhibitors of the epidermal growth factor receptor kinase , Janus kinase 2 kinase , and Src kinase did not block the effect . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
An essential role for Src kinase in ErbB receptor signaling through the MAPK pathway . ^^^ Surprisingly , Src inhibition affected neither association of Shc with ErbB receptors nor phosphorylation of receptor bound Shc . ^^^ Thus , ErbB signaling requires the engagement of a novel Src dependent route to MAPK , to trigger its rapid activation and subsequent efficient stimulation of transcription . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Signal therapy for RAS induced cancers in combination of AG 879 and PP 1 , specific inhibitors for ErbB 2 and Src family kinases , that block PAK activation . ^^^ CONCLUSION : These findings not only change our conventional view on the role of these RAS inducible ligands and ErbB family receptors ( serving as RAS activators ) but also suggest a new avenue for the treatment of RAS associated cancers by a combination of inhibitors specific for ERbB , Src , or PAK family kinases . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The interaction of the activated epidermal growth factor ( EGF ) receptor ( EGFR ) with the Src homology 2 ( SH 2 ) domain of Grb 2 ( growth factor receptor bound protein 2 ) initiates signalling through Ras and mitogen activated protein kinase . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Interaction of ouabain with the enzyme of the intact cells causes activation of Src , transactivation of EGFR , and activation of the Ras / ERK1 / 2 cascade . ^^^ These and previous findings indicate that ouabain induced activation of PKC and Ras , each linked to Na ( + ) / K ( + ) ATPase through Src / EGFR , are both required for the activation of ERK1 / 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Immunoprecipitation and Western blotting showed that the EGFR and Src were phosphorylated within 5 min of 10 ( 9 ) m ouabain stimulation . ^^^ Both ouabain induced DNA synthesis ( BrdUrd uptake ) and MAPK42 / 44 phosphorylation were inhibited by the Src inhibitor PP 2 , the EGFR kinase inhibitor AG 1478 , the tyrosine kinase inhibitor genistein , and the MEK 1 inhibitor PD 98059 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Src family kinase inhibitors PP 1 and PP 2 prevent tyrosine phosphorylation of beta 4 and disassembly of hemidesmosomes without interfering with the activation of EGF R . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Activation of extracellular signal regulated kinase by ultraviolet is mediated through Src dependent epidermal growth factor receptor phosphorylation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
H ( 2 ) O ( 2 ) induced promotion of eNOS activity and modulation of the eNOS phosphorylation status at Ser 1177 and Thr 495 were significantly attenuated by selective inhibitors of Src kinase , the ErbB receptor family , and phosphoinositide 3 kinase ( PI 3 K ) . ^^^ Together , these data indicate that H ( 2 ) O ( 2 ) promotes calcium dependent eNOS activity through a coordinated change in the phosphorylation status of the enzyme mediated by Src and ErbB receptor dependent PI 3 K activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Ang 2 increased the association of Pyk 2 with Src and with the epidermal growth factor receptor ( EGF R ) . ^^^ These findings indicate that Src and Pyk 2 act upstream of the EGF R and that the majority of Ang 2 induced ERK phosphorylation is dependent on trans activation of the EGF R . ^^^ Ang 2 induced ERK activation in C 9 cells is initiated by a PKCdelta dependent but Ca ( 2+ ) independent mechanism and is mediated by the Src / Pyk2 complex through trans activation of the EGF R . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Compared with their bicyclic 4 anilino 3 cyanoquinoline analogues , the tricyclic 4 anilino 3 cyanobenzo [ g ] quinolines are less active against EGF R kinase , equally active against MAPK kinase ( MEK ) , and more active against Src kinase . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
AVP induces extracellular signal related kinase ( ERK ) 1 ( p 44 ( mapk ) ) and ERK 2 ( p 42 ( mapk ) ) activation , a response prevented by treatment with mitogen activated protein kinase kinase ( MEK ) inhibitors ( PD 98059 and U 0126 ) , specific PKC inhibitors ( GF 1 and Ro 31 8220 ) , depletion of Ca ( 2+ ) ( EGTA and thapsigargin ) , selective epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( tyrphostin AG 1478 , compound 56 ) , or the selective Src family kinase inhibitor PP 2 . ^^^ Furthermore , AVP acts as a potent growth factor for IEC 18 cells , inducing DNA synthesis and cell proliferation through ERK , Ca ( 2+ ) , PKC , EGFR tyrosine kinase , and Src dependent pathways . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Binding of ouabain to Na ( + ) / K ( + ) ATPase activates tyrosine phosphorylation of the epidermal growth factor receptor ( EGFR ) , Src , and p42 / 44 mitogen activated protein kinases ( MAPKs ) in both cardiac myocytes and A7r5 cells . ^^^ Here , we explored the roles of Src and the EGFR in the ouabain invoked pathways that lead to the activation of MAPKs . ^^^ Significantly , both herbimycin A and PP 2 abrogated ouabain induced but not epidermal growth factor induced Src binding to the EGFR and the subsequent EGFR tyrosine phosphorylation . ^^^ These findings clearly indicate that ouabain transactivates the EGFR by activation of Src and stimulation of Src binding to the EGFR . ^^^ This resulted in increased binding of another adaptor protein Grb 2 to the Src EGFR complex and the subsequent activation of Ras and MAPKs . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In tumor cells , constitutive activation of STATs is linked to persistent activity of tyrosine kinases , including Src , epidermal growth factor receptor , Janus kinases , Bcr Abl , and many others . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Moreover , pretreatment with PP 2 , a selective inhibitor of the Src tyrosine kinase , attenuated both ISO mediated EGFR phosphorylation and ERK activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Upon stimulation of the bombesin receptors , KUZ increases the docking and activation of adaptors Src homology 2 domain containing protein and Gab 1 on the EGFR , and activation of Ras and Erk . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
On the other hand , within the protein tyrosine kinases involved in the phosphorylation of CaM are receptors with tyrosine kinase activity , such as the insulin receptor and the epidermal growth factor receptor , and nonreceptor protein tyrosine kinases , such as several members of the Src family kinases , Janus kinase 2 , and p38Syk . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The response to C5a was blocked by inhibitors of phosphatidylinositol 3 kinase , src kinase , and of the epidermal growth factor ( EGF ) receptor ( EGFR ) as well as by neutralizing Abs against the EGFR and heparin binding EGF like factor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
It was subsequently established that variation of the substituents on the 4 anilino group of the 6 , 7 dimethoxy 3 quinolinecarbonitrile changed the kinase specificity from EGFr to other kinases including Src and MEK . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We have shown previously that the muscarinic agonist , carbachol ( CCh ) , transactivates the epidermal growth factor receptor ( EGFr ) via calmodulin , Pyk 2 , and Src kinase activation . ^^^ Co incubation with the Src kinase inhibitor PP 2 and anti EGFr had an additive inhibitory effect on CCh induced ERK phosphorylation greater than either inhibitor alone . ^^^ We conclude that CCh stimulated EGFr transactivation and subsequent ERK activation , a pathway that limits CCh induced chloride secretion , is mediated by metalloproteinase dependent extracellular release of TGF alpha and intracellular Src activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Non receptor and receptor tyrosine kinases , such as Src and EGF receptor ( EGFR ) , are major inducers of vascular endothelial growth factor ( VEGF ) , one of the most potent mediators of angiogenesis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Src dependent tyrosine phosphorylation regulates dynamin self assembly and ligand induced endocytosis of the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Several inhibitors of epidermal growth factor receptor ( EGFR ) kinase and Src family kinases ( SFK ) were employed to study the role of these kinases in EGFR internalization through clathrin coated pits . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The signaling pathways that are rapidly elicited by the interaction of ouabain with Na ( + ) / K ( + ) ATPase , and are independent of changes in intracellular Na ( + ) and K ( + ) concentrations , include activation of Src kinase , transactivation of the epidermal growth factor receptor by Src , activation of Ras and p42 / 44 mitogen activated protein kinases , and increased generation of reactive oxygen species by mitochondria . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
AG 1478 also failed to reverse IFN gamma induced tyrosine phosphorylation of the EGFr , but receptor phosphorylation was attenuated by both the neutralizing antibody to TGF alpha and PP 2 , a Src kinase inhibitor . ^^^ The release of TGF alpha and intracellular Src activation likely combine to mediate EGFr phosphorylation , but only Src appears to contribute to the inhibition of transport . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Src family inhibitor PP 1 and the epidermal growth factor receptor kinase inhibitor AG 1478 did not alter alpha ( 2 ) AR contraction , whereas the mitogen activated protein kinase extracellular signal regulated kinase kinase inhibitor PD 98059 attenuated the contraction . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Activation of PAR 1 leads to an increase in Src , Fyn , and epidermal growth factor receptor ( EGFR ) phosphorylation , with EGFR receptor transactivation by Src family kinases the major mechanism for PAR 1 dependent activation of extracellular signal regulated kinase , p 38 mitogen activated protein kinase , and protein kinase B . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Caveolin 1 phosphorylation in human squamous and epidermoid carcinoma cells : dependence on ErbB 1 expression and Src activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Src and epidermal growth factor receptor ( EGFR ) stimulated cell motility is dependent upon calpain activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
CCh induced p 38 phosphorylation was attenuated by the EGFR inhibitor tyrphostin AG 1478 ( 0 . 1 nM 10 microM ) and by the Src family kinase inhibitor PP 2 ( 20 nM 2 microM ) . ^^^ We conclude that Ca ( 2+ ) dependent agonists stimulate p 38 MAPK in T ( 84 ) cells by a mechanism involving intracellular Ca ( 2+ ) , Src family kinases , and the EGFR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Phenylephrine stimulated tyrosine phosphorylation of the EGFR , whereas carbachol stimulated p 60 ( Src ) , and possibly Pyk 2 , to activate MAPK . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
ACh induced Akt activation was blocked by the Src tyrosine kinase inhibitor 4 amino 5 ( 4 chlorophenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyrimidine ( PP 2 ) and by 4 ( 3 chloroanilino ) 6 , 7 dimethoxyquinazoline ( AG 1478 ) , an epidermal growth factor receptor ( EGFR ) inhibitor , suggesting phosphorylation of a receptor tyrosine kinase in an Src tyrosine kinase dependent manner . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Additionally , the general tyrosine kinase inhibitor genistein , as well as the Src inhibitor PP 1 and the epidermal growth factor receptor kinase inhibitor 4 ( 3 chloroanilino ) 6 , 7 dimethoxyquinazoline ( AG 1478 ) , inhibited receptor mediated activation of ERK , suggesting a role for tyrosine kinases . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Aplidin induced a specific cellular stress response program , including sustained activation of the epidermal growth factor receptor ( EGFR ) , the non receptor protein tyrosine kinase Src , and the serine / threonine kinases JNK and p 38 MAPK . ^^^ Aplidin induced apoptosis was only partially blocked by the general caspase inhibitor benzyloxycarbonyl VAD fluoromethyl ketone and was also sensitive to AG 1478 ( an EGFR inhibitor ) , PP 2 ( an Src inhibitor ) , and SB 203580 ( an inhibitor of JNK and p 38 MAPK ) in MDA MB 231 cells . ^^^ The intracellular level of GSH affected Aplidin action ; pretreatment of cells with GSH or N acetylcysteine inhibited , whereas GSH depletion caused , hyperinduction of EGFR , Src , JNK , and p 38 MAPK . ^^^ Aplidin induces apoptosis in human cancer cells via glutathione depletion and sustained activation of the epidermal growth factor receptor , Src , JNK , and p 38 MAPK . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
HU 210 induced ERK activation was inhibited by tyrphostin AG 1478 and PP 2 , widely employed inhibitors of the epidermal growth factor receptor ( EGF ( R ) ) and the Src family of cytosolic tyrosine kinases , respectively . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Finally , to understand the mechanisms of resistance to EGF R inhibitors , which have been shown to be useful in many different types of cancer , the Src STAT signaling pathways are described here in detail . ^^^
Interacting proteins: P12931 and P00533	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 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These results suggested that nicotine induces the activation of both PI 3 kinase / Akt and ERK pathways via common pathways including non alpha 7 nAChRs , L type VSCC , CaM kinase 2 and EGFR in PC12h cells , but Src family tyrosine kinases only participate in the pathway to activate Akt . . ^^^ Nicotine induced phosphorylation of Akt through epidermal growth factor receptor and Src in PC12h cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
RESULTS : Studies of receptor type specificity showed that SMA 41 : ( a ) preferentially inhibited the kinase activity of EGFR over those of Src , insulin receptor and protein kinase C ( PKC , a serine / threonine kinase ) , ( b ) induced stronger inhibition of growth stimulated with EGF than of growth stimulated with platelet derived growth factor ( PDGF ) or fetal bovine serum ( FBS ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Further studies implicate Src and epidermal growth factor receptor ( EGFR ) kinase activity in the PAR 4 dependent p 38 mitogen activated protein kinase signaling pathway . ^^^ Thrombin phosphorylates EGFRs and ErbB 2 via a PP 1 sensitive pathway in PAR 1 ( / ) cells that stably overexpress PAR 4 ; the Src mediated pathway for EGFR / ErbB2 transactivation underlies the protracted phases of thrombin dependent extracellular signal regulated kinase activation in PAR 1 ( / ) cells that overexpress PAR 4 and in cardiomyocytes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Additionally , stretch induced increases in both ERK phosphorylation and force generation were attenuated by inhibition of tyrosine kinases ( genistein ) , src ( PP 2 ) , and specific sites on the epidermal growth factor receptor ( EGFR ) ( AG 1478 ) . ^^^ In summary , stretch seems to enhance force generation via ERK signaling through an EGFR / src dependent mechanism activated by peroxide derived from a stretch mediated activation of the NAD ( P ) H oxidase , a response that may contribute to hypertensive alterations in vascular reactivity . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The requirement of Tyr 319 seems specific for EGFR because Ang 2 induced activation of other tyrosine kinases , including Src and JAK 2 , was preserved in cells expressing AT 1 Y319F . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Moreover , we showed that both isoforms activate ERK phosphorylation in an Src kinase dependent manner , whereas PKC was mainly implicated in ERK activation and EGFR phosphorylation by TP beta . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Combined cell lysates were affinity purified over the SH 2 domain of the adapter protein Grb 2 ( GST SH 2 fusion protein ) that specifically binds phosphorylated EGFR and Src homologous and collagen ( Shc ) protein . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Development of an efficient `` substrate trapping ' ' mutant of Src homology phosphotyrosine phosphatase 2 and identification of the epidermal growth factor receptor , Gab 1 , and three other proteins as target substrates . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Upon activation of the receptor for the epidermal growth factor ( EGFR ) , Sprouty 2 undergoes phosphorylation at a conserved tyrosine that recruits the Src homology 2 domain of c Cbl . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Ouabain binding to Na ( + ) / K ( + ) ATPase activates Src / epidermal growth factor receptor ( EGFR ) to initiate multiple signal pathways that regulate growth . ^^^ Isolated rat cardiac caveolae contained Src , EGFR , ERK1 / 2 , and 20 30 % of cellular contents of alpha ( 1 ) and alpha ( 2 ) isoforms of Na ( + ) / K ( + ) ATPase , along with nearly all of cellular caveolin 3 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Recently , studies have shown that MUC 1 interacts with beta catenin , erbB receptors , src , GSK 3beta and protein kinase Cdelta , possibly in a complex that promotes the disassembly of adherens junctions and the invasion of cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Src inhibitor PP 1 and the EGFR inhibitor AG 1478 completely inhibited carbachol stimulated MAPK activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Roles of Src and epidermal growth factor receptor transactivation in transient and sustained ERK1 / 2 responses to gonadotropin releasing hormone receptor activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Besides coupling with heterotrimeric G proteins to activate phospholipase C beta ( PLC beta ) , AT1R also activates receptor tyrosine kinases ( PDGF R , EGF R and IGF R ) and non receptor tyrosine kinases ( Src , Fyn , Yes , proline rich tyrosine kinase 2 ( Pyk 2 ) , focal adhesion kinase ( FAK ) and JAK 2 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This activation of p130Cas was also abrogated by the tetrapeptide RGDS , which disrupts integrin heterodimerization ; cytochalasin D , which depolymerizes the actin cytoskeleton ; or a selective Src family kinase inhibitor , PP 2 , but not by an EGFR inhibitor , AG 1478 . ^^^ 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 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Here , using specific antibodies and inhibitors , we investigated the thrombin induced phosphorylation of Src family kinases , nonreceptor proline rich tyrosine kinase ( Pyk 2 ) , EGFR , and ERK1 / 2 . ^^^ Our results show that Src and Pyk 2 are involved upstream of the EGFR transactivation that is required for ERK1 / 2 phosphorylation . ^^^ Moreover , only after BAPTA AM pretreatment was thrombin induced activation of ERK1 / 2 partially preserved from the effects of EGFR and PKC inhibition but not Src family kinase inhibition . ^^^ These results suggest that BAPTA , by preventing [ Ca2+ ] 1 elevation , unmasks a new pathway of Src family kinase dependent thrombin stimulated ERK1 / 2 phosphorylation that is independent of EGFR and PKC activation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
At least some of this increased CD 44 expression results from elevated EGFR levels through a Src dependent mechanism , consistent with the notion that EGFR promotes constitutive Src activation in MPNSTs . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Interestingly , NT did not stimulate epidermal growth factor receptor transactivation , and epidermal growth factor receptor tyrosine kinase or Src inhibitors did not affect NT induced ERK activation in PANC 1 cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Binding of ouabain to Na / K ATPase changes the interaction of the enzyme with neighboring membrane proteins and induces the formation of multiple signaling modules , resulting in activation of Src , transactivation of the EGF receptor ( EGFR ) , and increased production of reactive oxygen species ( ROS ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In biochemical assays , SU 10944 exhibits potent inhibitory activity against VEGFR 1 ; weak activity against other related subgroup members , including stem cell factor receptor ( SCFR ) , platelet derived growth factor receptor beta ( PDGFRbeta ) , and fibroblast growth factor receptor 1 ( FGFR 1 ) ; and no detectable activity against other protein tyrosine kinases such as epidermal growth factor receptor ( EGFR ) , Src , and hepatocyte growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The SRC homology 2 domain of Rin 1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Overexpression of receptor tyrosine kinases including the epidermal growth factor receptor ( EGF R ) as well as nonreceptor tyrosine kinases , such as Src , have been implicated in the formation of human lung cancers . ^^^ Furthermore , the stimulation of Stat 3 DNA binding activity by EGF requires the activity of EGF R tyrosine kinase as well as Src kinase , while the upregulation of Stat 3 activity by IL 6 or HGF requires only Src kinase activity . ^^^ These results demonstrate a role of Stat 3 in transducing survival signals downstream of tyrosine kinases such as Src , EGF R , and c Met , as well as cytokines such as IL 6 , in human nonsmall cell lung cancers . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Our results point to the involvement of several ErbB specific ligands ( amphiregulin and neuregulin 1 ) and enzymes or adaptor molecules ( PI3K , Src , Shc and Grb 7 ) in the ErbB pathway dysregulation associated with breast cancer . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Both the effects of HNP 1 3 on wound closure and ERK1 / 2 activation were blocked by specific inhibitors of the mitogen activated protein kinase kinase MEK , whereas inhibitors of epidermal growth factor receptor tyrosine kinase , phosphatidylinositol 3 kinase , and Src did block defensin enhanced wound closure but not ERK1 / 2 activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Both the dominant negative form of the EGFR ( HER CD 533 ) and the EGFR TK inhibitor ZD 1839 ( Iressa ) abrogated cellular invasion induced by pS 2 , spasmolytic polypeptide ( SP ) and the src oncogene , but not by ITF and the TXA 2 R . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Phosphorylation of cortactin tyrosine 421 and 466 was elevated in response to Src , epidermal growth factor receptor and Rac 1 activation , and tyrosine 421 phosphorylated cortactin localized with F actin in lamellipodia and podosomes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Moreover , GnRH induced phosphorylation of ERK1 / 2 and expression of c fos in HEK 293 cells is independent of Src and EGF R transactivation , and is mediated through the PKC / Raf / MEK cascade . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Consistent with this , PPAR agonists increased tyrosine autophosphorylation of the EGFR as well as phosphorylation at a putative Src specific site , Tyr 845 . ^^^ Experiments with the Src inhibitor , PP 2 , and the antioxidant N acetyl L cysteine revealed critical roles for Src and reactive oxygen species as upstream mediators of EGFR transactivation in response to PPAR ligands . ^^^ In contrast , p 38 activation by PPARalpha and gamma ligands occurred independently of Src , oxidative stress , the EGFR , and Ras . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We have previously shown that exposure to zinc ions can activate epidermal growth factor ( EGF ) receptor ( EGFR ) signaling in murine fibroblasts and A 431 cells through a mechanism involving Src kinase . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
EGF ( epidermal growth factor ) binding to its receptor ( EGFR ) induces dimerization and autophosphorylation of the receptor at multiple tyrosine residues , which serve as docking sites for recruitment of proteins with SH 2 ( Src homology 2 ) domains that activate multiple downstream signalling pathways . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The specific blockade of phosphorylation at Tyr 845 with Src family kinase inhibition and at Tyr 1148 with phosphatidylinositol 3 kinase inhibition suggests that GM 3 inhibits integrin induced , ligand independent EGFR phosphorylation ( cross talk ) through suppression of Src family kinase and phosphatidylinositol 3 kinase signaling . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Consistent with this observation , H2O2 stimulated EGFR tyrosine phosphorylation was abolished by specific Src kinase family inhibitor CGP 77675 , implicating Src in H2O2 induced EGFR activation . ^^^ Herein , we postulate also that H2O2 induced STAT activation in carcinoma cells involves Src dependent EGFR transactivation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Addition of galardin to cells stimulated with bombesin or LPA specifically inhibited total EGFR phosphorylation , as well as site specific phosphorylation of tyrosine 845 , a putative Src phosphorylation site , and tyrosine 1068 , a typical autophosphorylation site . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Bradykinin caused activation of p60Src and Src dependent phosphorylation of the EGFR on Tyr 845 in lipid rafts , as well as recruitment of phospholipase C ( PLC ) gamma 1 to the rafts . ^^^ Depletion of cholesterol by methyl beta cyclodextrin disrupted the raft localization of EGFR and Src , as well as bradykinin induced translocation of PLCgamma 1 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
EGFR , ErbB 2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene mediated transformation . ^^^ In this study , we show that H Ras , N Ras , K Ras , EGFR and ErbB 2 but not 5 Src suppress RhoB promoter transcriptional activity in NIH3T3 cells and human cancer cell lines derived from lung ( A 549 ) , pancreatic ( Panc 1 ) and cervical ( C33A ) tumors . ^^^ Ectopic expression of RhoB , but not the closely related family member RhoA , antagonizes the ability of EGFR , ErbB 2 , H Ras , N Ras and K Ras but not 5 Src to transform NIH3T3 cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
A mutant P2Y ( 2 ) receptor lacking the PXXP motifs was found to stimulate calcium mobilization and serine / threonine phosphorylation of the Erk1 / 2 mitogen activated protein kinases , like the wild type receptor , but was defective in its ability to stimulate tyrosine phosphorylation of Src and Src dependent tyrosine phosphorylation of the proline rich tyrosine kinase 2 , epidermal growth factor receptor ( EGFR ) , and platelet derived growth factor receptor . ^^^ Dual immunofluorescence labeling of the P2Y ( 2 ) receptor and the EGFR indicated that UTP caused an increase in the co localization of these receptors in the plasma membrane that was prevented by the Src inhibitor PP 2 . ^^^ Together , these data suggest that agonist induced binding of Src to the SH 3 binding sites in the P2Y ( 2 ) receptor facilitates Src activation , which recruits the EGFR into a protein complex with the P2Y ( 2 ) receptor and allows Src to efficiently phosphorylate the EGFR . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
A tyrosine phosphorylated peptide of the epidermal growth factor receptor specifically retrieved the Src homology domain ( SH ) 2 and SH 3 domain containing adapter protein Grb 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Promising therapeutic targets for cancer metastasis have been identified , including Src , focal adhesion kinase , the integrin receptor , the vascular endothelial growth factor receptor , the epidermal growth factor receptor , Her 2 / neu , c Met , Ras / Rac GTPases , Raf kinase , farnesyl diphosphate synthase ( i . e . , amino bisphosphonate therapeutic target ) and matrix metalloproteases within the context of their implicated functional roles in cancer growth , invasion , angiogenesis and survival at secondary sites . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In the present work , we found for the first time that uPAR stimulation with the amino terminal fragment ( ATF ) of urokinase devoid of proteolytic activity transactivates the EGFR in mammary MCF 7 cells through a mechanism involving Src and a metalloproteinase , as indicated by its sensitivity to selected inhibitors . ^^^ All this reveals novel regulatory systems operating through autocrine loops involving uPAR stimuli , Src , MMP and EGFR activation which could mediate fine control of physiological processes as well as contribute to the expression of proliferative and invasive phenotypes of cancerous cells . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Src dependent ERK 5 and Src / EGFR dependent ERK1 / 2 activation is required for cell proliferation by asbestos . ^^^ In contrast to rapid and transient activation of extracellular signal regulated kinase 5 ( ERK 5 ) by EGF or H2O2 , asbestos caused protracted oxidant dependent ERK 5 activation that was inhibited by an Src kinase inhibitor ( PP 2 ) , but not by an inhibitor of epidermal growth factor receptor ( EGFR ) phosphorylation ( AG 1478 ) . ^^^ Time frame studies indicated immediate activation of Src by asbestos fibers , whereas EGFR phosphorylation occurred subsequently . ^^^ Data suggest that asbestos causes activation of ERK 5 through an EGFR independent pathway , whereas ERK1 / 2 activation is dependent on Src through a mechanism involving phosphorylation of the EGFR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
HA Ras ( N 17 ) ) partially inhibited the ATP and PDBu induced activation of ERK1 / 2 and blocked ionomycin and EGF stimulated ERK1 / 2 , and inhibition of tyrosine kinases with AG 1478 , an EGFR inhibitor , or the src family kinase inhibitor PP 2 attenuated ATP stimulated ERK1 / 2 activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Addition of the epidermal growth factor receptor ( EGFR ) inhibitors PP 3 or AG 490 or the Src kinase inhibitor PP 2 blocked the SOCS 2 induced neurite outgrowth . ^^^ The overexpressed SOCS 2 bound to the EGFR , which was constitutively phosphorylated at Tyr 845 , the Src binding site . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Blockade of the epidermal growth factor receptor , beta 1 integrin , or Src significantly inhibited neuronal differentiation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Although A 431 cells display significant activation of both EGFR and Src kinases , our data suggest that these account for only a fraction of the steady state activity that targets p 120 Y228 , and that Src family kinases are not necessary intermediates for epidermal growth factor induced signaling to p 120 Y228 . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In both THP 1 and transfected COS 7 cells , pretreatment of the selective Src family kinase inhibitor pyrazolopyrimidine PP 1 abolished the JNK activation , whereas the epidermal growth factor receptor inhibitor AG 1478 [ N ( 3 chlorophenyl ) 6 , 7 dimethoxy 4 quinazolinanine ] failed to do that . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Differential effects of tyrosine kinase inhibitors on volume sensitive chloride current in human atrial myocytes : evidence for dual regulation by Src and EGFR kinases . ^^^ Furthermore , the selective Src family PTK inhibitor PP 2 ( 5 microM ) stimulated 1 ( Cl . vol ) , mimicking genistein , whereas the selective EGFR ( ErbB 1 ) kinase inhibitor tyrphostin B 56 ( AG 556 , 25 microM ) reduced 1 ( Cl . vol ) , mimicking A 23 and A 25 . ^^^ Src and EGFR kinases , distinct soluble and receptor mediated PTK families , have opposing effects on 1 ( Cl . vol ) , and multiple target proteins are likely to be involved . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Src family kinase Yes triggers hyperosmotic activation of the epidermal growth factor receptor and CD 95 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
S1P stimulated transactivation of EGFR and PDGFbetaR was dependent on Src , reactive oxygen species , and cholesterol rich membranes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Endothelin 1 induced NGF augmentation was mediated by the endothelin A receptor , Gibetagamma , PKC , the Src family , EGFR , extracellular signal regulated kinase , p38MAPK , activator protein 1 , and the CCAAT / enhancer binding protein delta element . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Inhibitors were employed to determine pathway ( ER , EGFR , membrane organization , PI 3 kinase , Src kinase , Ca2+ ) involvement and timing of pathway activations ; all affected ERK activation as early as 3 6 min , suggesting simultaneous , not sequential , activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The acinar cell phospholipid secretory responses to isoproterenol , moreover , were inhibited by PP 2 , a selective inhibitor of tyrosine kinase Src responsible for ligand independent EGFR phosphorylation . ^^^ Taken together , our data are the first to demonstrate the requirement for Src kinase dependent EGFR transactivation in regulation of salivary phospholipid secretion in response to beta adrenergic GPCR activation . . ^^^ Salivary phospholipid secretion in response to beta adrenergic stimulation is mediated by Src kinase dependent epidermal growth factor receptor transactivation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Aplidin is an antitumor drug that induces apoptosis and activates EGFR , Src , JNK and p38MAPK . ^^^ Concordantly , Aplidin increases AP 1 and NF kappaB activity . c FOS induction depends on EGFR , Src and JNK / p38MAPK . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Although the Tyr 319 residue of the AT 1 R has been proposed to be an essential regulator of EGF R transactivation , stimulation of wild type and mutant ( Y319F ) AT 1 R expressed in COS 7 cells caused EGF R transactivation and subsequent ERK1 / 2 phosphorylation through release of HB EGF in a Src dependent manner . ^^^ In contrast , the noninvolvement of MMPs in HEK 293 cells , which may reflect the absence of Src activation by Ang 2 , was associated with lack of transactivation of the EGF R . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We present here a study of cardiac and renal hypertrophy induced by ouabain infused into rats for prolonged periods and relate this effect to the recently described ouabain induced activation of the Src EGFr ERK signaling pathway . ^^^ These effects in vivo are associated with a significant enrichment of alpha 1 , beta 1 , gammaa Na K ATPase subunits together with Src and EGFr in isolated renal caveolae membranes and activation of ERK1 / 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Nicotine induces the activation of both PI 3 kinase / Act and ERK / CREB pathways via common pathways including non alpha 7 nAChRs , L type VSCC , CaM kinase and EGFR in PC12h cells , but Src family tyrosine kinases only participate in the pathway to activate Akt . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Exposure of primary cultures of rabbit renal proximal tubular cells to hydrogen peroxide ( H ( 2 ) O ( 2 ) ) stimulated Src , EGFR , ERK1 / 2 , and Akt activation in a time dependent manner as determined by the phosphorylation of each protein . ^^^ The Src inhibitor PP 1 completely blocked EGFR , ERK1 / 2 , and Akt phosphorylation following H ( 2 ) O ( 2 ) exposure . ^^^ In contrast , blockade of the EGFR by AG 1478 inhibited phosphorylation of ERK1 / 2 but not Src or Akt phosphorylation following H ( 2 ) O ( 2 ) exposure . ^^^ These results suggest that Src mediates H ( 2 ) O ( 2 ) induced EGFR transactivation . ^^^ H ( 2 ) O ( 2 ) and EGF induced ERK1 / 2 activation is mediated by EGFR , whereas Akt is activated by Src independent of EGFR following H ( 2 ) O ( 2 ) exposure . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Moreover , the inhibitory effect of ciglitazone on the LPS induced reduction in mucin synthesis and upregulation in apoptosis , caspase 3 activity , and NO generation was blunted by a selective inhibitor of tyrosine kinase Src , PP 2 , responsible for ligand independent EGFR transactivation . ^^^ These findings indicate that PPARgamma activation leading to the suppression of P . gingivalis LPS inhibition of salivary mucin synthesis involves Src kinase dependent EGFR transactivation . . ^^^ Src kinase dependent epidermal growth factor receptor transactivation in PPARgamma ligand induced suppression of Porphyromonas gingivalis interference with salivary mucin synthesis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Neither AG 1478 , an epidermal growth factor receptor kinase inhibitor , nor AG 1295 , a platelet derived growth factor receptor kinase inhibitor , had any effect on Ang 2 stimulated Src activity , MAPK activation , or eNOS expression . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Second , through the use of the Src inhibitor PP 1 , our findings establish EGFR movement out of the early endosomes as the exact location where c Cbl mediated ubiquitinylation is essential for EGFR trafficking . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The Src family kinase Yes and the tyrosine phosphatase SHP 2 were detected in immunoprecipitates using either anti PYK 2 or anti EGFR antibodies . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This effect occurs by activation of Src and the epidermal growth factor receptor ( EGFR ) , and thus supports the concept of an additional , nonionic , transducing function of the Na pump . ^^^ Thus ouabain activated the recruitment of both the Na pump alpha 1 subunit and EGFR in the caveolae from rat A7r5 cells , whereas in both human and canine cells , ouabain activated the recruitment of Src , with the caveolar content of the other proteins remaining constant . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
It has been reported that Src family kinases are activated by G protein coupled receptors ( GPCRs ) , followed by downstream EGFR and MAPK activation . ^^^ To further elucidate the mechanism of activation of EGFR by GRP in HNSCC , we investigated the role of Src family kinases . ^^^ Blockade of Src family kinases using an Src specific tyrosine kinase inhibitor A 419259 decreased GRP induced EGFR phosphorylation and MAPK activation . ^^^ These results suggest that Src family kinases contribute to GRP mediated EGFR growth and invasion pathways by facilitating cleavage and release of TGF alpha and amphiregulin in HNSCC . . ^^^ SRC family kinases mediate epidermal growth factor receptor ligand cleavage , proliferation , and invasion of head and neck cancer cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We tested this hypothesis by using a simplified model for the epidermal growth factor receptor pathway substrate 8 src homology 3 domain protein , both of whose monomeric and domain swapped structures have been solved . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
LPA equally protected B82L cells , or transfectants expressing EGFR , the kinase dead EGFR ( K721A ) , EGFR ( Y5F ) receptor mutant , which lacks five autophosphorylation sites , or EGFR ( Y845F ) , which lacks the Src phosphorylation site from tumor necrosis factor alpha induced apoptosis . ^^^ EGFR with or without intrinsic kinase activity or without the Src phosphorylation site augmented , but was not required for , LPA elicited cell proliferation or migration . ^^^ In EGFR ( Y5F ) expressing cells , LPA failed to elicit tyrosine phosphorylation of Src homologous and collagen protein ( SHC ) and caused only a modest increase in ERK1 / 2 phosphorylation similar to that in wild type B82L cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In contrast , activation of focal adhesion kinase , Src , and protein kinase C , adhesion to matrix proteins , cell spreading , migration , and actin cytoskeletal rearrangements are induced independently of EGFR kinase activity . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
GM 6001 , a matrix metalloproteinase inhibitor , and PP 2 , a Src family protein kinase inhibitor , suppressed 15 d PGJ 2 and TZDs induced phosphorylation of EGF R and PDGFbeta R as well as activation of ERK1 / 2 and Akt . ^^^ These data suggest that 15 d PGJ 2 and TZDs activate PI 3 K / ERK pathway through Src family kinase and matrix metalloproteinase dependent transactivation of EGF R and PDGF R . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Interestingly , pharmacological inhibition of the kinase activities of EGFR , erbB 2 , and src and activation of mitogen activated protein kinase , but not phosphatidylinositol 3 ' kinase , significantly up regulated SIRPalpha 1 promoter activity . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The gastric mucosal phospholipid secretory responses to isoproterenol , furthermore , were inhibited by PP 2 , a selective inhibitor of tyrosine kinase Src responsible for ligand independent EGFR phosphorylation , but not by ERK inhibitor , PD 98059 . ^^^ The findings underline the central role of EGFR in mediation of gastric mucosal secretory processes , and demonstrate the requirement for Src kinase dependent EGFR transactivation in regulation of gastric mucosal phospholipid secretion in response to beta adrenergic GPCR activation . . ^^^ Secretion of gastric mucus phospholipids in response to beta adrenergic G protein coupled receptor activation is mediated by SRC kinase dependent epidermal growth factor receptor transactivation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Finally , PAR 1 activation induces Src phosphorylation , which is reversed by using the Src tyrosine kinase inhibitor PP 2 , suggesting that Src activation plays a permissive role for PAR 1 mediated ERK1 / 2 activation and cell proliferation probably acting downstream of the EGFR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
CCh also induced association of FAK with the EGFr and FAK phosphorylation was attenuated by an EGFr inhibitor , tyrphostin AG 1478 , and an inhibitor of Src family kinases , PP 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
PDGFR , not FAK or EGFR , appears to be the upstream protein tyrosine kinase responsible for the detachment induced Src activation in the lung tumor cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The inhibition of tumor cell proliferation is not associated with blockage of EGF receptor ( EGFR ) , but substantially due to the interference with the signalling pathway at the level of Src tyrosine kinase and at the level of the downstream effector signal mitogen activated protein kinases ( MAPKs ) , ERK 1 2 . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
RESULTS : The proapoptotic bile salts taurolithocholate 3 sulfate ( TLCS ) , glycochenodesoxycholate ( GCDC ) and taurochenodeoxycholate ( TCDC ) , but not taurocholate ( TC ) , activate within 1 minute the Src kinase family member Yes , followed by an association of Yes with EGFR and subsequent EGFR activation . ^^^ CONCLUSIONS : The data identify the Src kinase Yes as an upstream target of proapoptotic bile acids , which triggers EGFR activation , subsequent CD 95 tyrosine phosphorylation , and apoptosis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The acinar cell secretory responses to isoproterenol , furthermore , were blunted in a concentration dependent fashion by PP 2 , a selective inhibitor of tyrosine kinase Src responsible for ligand independent EGFR autophosphorylation . ^^^ Our findings underline the role of EGFR as a convergence point in modulation of salivary mucin secretion triggered by beta adrenergic agonist GPCR activation and demonstrate the importance of Src kinase in the EGFR transactivation process . . ^^^ Src kinase dependent epidermal growth factor receptor transactivation in salivary mucin secretion in response to beta adrenergic G protein coupled receptor activation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Phosphorylation of Alix by Src caused it to translocate from the membrane and cytoskeleton to the cytoplasm and reduced its interaction with binding partners SETA / CIN85 , epidermal growth factor receptor , and Pyk 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
To verify that ME activates EGFR and to determine the involvement of Src , Western blotting of EGFR was performed after ME administration with and without herbimycin A . ^^^ We conclude that ME induced cardioprotection is mediated via Src dependent EGFR transactivation and activation of the PI3K and MAPK pathways . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In addition to this pathway , the non receptor tyrosine kinases ( Src ) , EGF receptor ( EGFR ) , and phosphatidylinositol 3 kinase ( PI 3 K ) have been implicated in linking a variety of G protein coupled receptors to MAPK cascades . ^^^ We initially observed that BK and EGF dependent activation of Src , EGFR , Akt , and p42 / p44 MAPK and [ 3H ] thymidine incorporation were mediated by Src and EGFR , because the Src inhibitor PP 1 and EGFR kinase inhibitor AG 1478 abrogated BK and EGF dependent effects . ^^^ These results suggest that , in VSMCs , the mechanism of BK stimulated activation of p42 / p44 MAPK and cell proliferation was mediated , at least in part , through activation of Src family kinases , EGFR transactivation , and PI 3 K / Akt . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The reduction in EGFR levels and EGF induced signaling in SOCS 5 expressing cells requires both the Src homology 2 and SOCS box domains of SOCS 5 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
At the same concentrations , ouabain 1 ) activated Src kinase and stimulated the interaction of Src and Na+ / K+ ATPase with epidermal growth factor receptor ( EGFR ) ; 2 ) caused a transient and then a sustained activation of extracellular signal regulated kinases 1 and 2 ( ERK1 / 2 ) ; 3 ) increased the expression of p21Cip1 but decreased that of p 53 ; and 4 ) activated c Jun NH 2 terminal kinase ( JNK ) but not p 38 kinase . ^^^ These data , in conjunction with our previous findings on the signaling role of Na+ / K+ ATPase in other cells , suggest that ouabain induced activation / transactivation of Src / EGFR by Na+ / K+ ATPase leads to activation of ERK1 / 2 , the resulting increase in the level of cell cycle inhibitor p21Cip1 , and growth arrest . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The EGF induced GRK 2 EGFR complex formation was greatly reduced by perturbation of EGFR and Src tyrosine kinase activity . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
However , EGFR endocytosis was rescued in Grb 2 depleted cells by chimeric proteins consisting of the Src homology ( SH ) 2 domain of Grb 2 fused to c Cbl . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Pretreatment of cells with inhibitors of PI3K , Src family tyrosine kinases , and EGFR also decreased HUVEC migration . ^^^ In conclusion , these results suggest that Ang 2 mediates an increase in FAK and paxillin phosphorylation and induces HUVEC migration through signal transduction pathways dependent on PI3K and Src tyrosine kinase activation and EGFR transactivation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The squamous carcinoma cell line HN 5 , which overexpresses EGF receptor and displays sustained receptor kinase activation , was used as a model system , where pharmacological inhibition of EGF receptor kinase by erlotinib markedly reduced auto and substrate phosphorylation , Src family phosphorylation at EGFR Y 845 , while increasing total EGF receptor protein . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Adhesion to fibronectin induced PLC gamma 1 tyrosine phosphorylation that was inhibited by a Src kinase inhibitor , but not an epidermal growth factor receptor kinase inhibitor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Antagonistic regulation of swelling activated Cl current in rabbit ventricle by Src and EGFR protein tyrosine kinases . ^^^ To determine whether protein tyrosine kinase ( PTK ) modulates 1 ( Cl , swell ) and to identify the PTK involved , we studied the effects of a broad spectrum PTK inhibitor ( genistein ) , selective inhibitors of Src ( PP 2 , a pyrazolopyrimidine ) and epidermal growth factor receptor ( EGFR ) kinase ( PD 153035 ) , and a protein tyrosine phosphatase ( PTP ) inhibitor ( orthovanadate ) . 1 ( Cl , swell ) evoked by hyposmotic swelling was increased 181 + / 17 % by 100 microM genistein , and the genistein induced current was blocked by the selective 1 ( Cl , swell ) blocker tamoxifen ( 10 microM ) . ^^^ In contrast with block of Src , block of EGFR kinase with PD 153035 ( 20 nM ) inhibited 1 ( Cl , swell ) . ^^^ The results indicate that tyrosine phosphorylation controls 1 ( Cl , swell ) , and regulation of 1 ( Cl , swell ) by the Src and EGFR kinase families of PTK is antagonistic . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We report that tissue type plasminogen activator ( tPA ) elicited tyrosine phosphorylation and cytosolic accumulation of an active ( non serine threonin phosphorylated , nonubiquitinated ) form of beta catenin in ECV 304 carcinoma cells . tPA dependent beta catenin activation is mediated through epidermal growth factor receptor ( EGFR ) transactivation ( via Src ) , suggested by the inhibitory effects of AG 1478 and PP 2 ( specific inhibitors of EGFR and Src , respectively ) and by the lack of beta catenin activation in EGFR negative B 82 fibroblasts . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The LPS induced reduction in mucin synthesis , furthermore , was countered by PD 153035 ( 76 . 8 % ) , a specific inhibitor of EGFR kinase as well as PP 2 ( 54 . 7 % ) , a selective inhibitor of tyrosine kinase Src responsible for ligand independent EGFR transactivation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Exogenously administered reactive oxygen species ( ROS ) were found to activate ERK1 / ERK2 via the EGFR and src tyrosine kinase activity and pretreatment of cells with the antioxidant N acetylcysteine ( NAC ) and the NADPH oxidase inhibitor DPI abrogated albumin induced activation of ERK1 / ERK2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
RESULTS : In wild type LLC PK 1 cells , depletion of cholesterol by methyl beta cyclodextrin reduced ouabain induced accumulation of Na / K ATPase alpha 1 subunit , EGFR , Src , and MAPKs in clathrin coated vesicles , as well as in endosomes . ^^^ Depletion of caveolin 1 also significantly reduced the ouabain induced accumulation of Na / K ATPase alpha 1 subunit , EGFR , Src , and MAPKs in clathrin coat vesicles , as well as early and late endosomes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In breast cancer , Src activates matrix metalloproteinase 2 and 9 , which cleaves heparin binding epidermal growth factor , and thus activates EGFR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In cultured bovine adrenal glomerulosa cells , LPA , which is predominantly coupled to Gi and partially to Gq / protein kinase C alpha and epsilon , caused phosphorylation of Src ( at Tyr 416 ) , proline rich tyrosine kinase ( Pyk 2 at Tyr 402 ) , EGF R , protein kinase B / Akt , extracellularly regulated signal kinases 1 / 2 , and their dependent protein , p 90 ribosomal S 6 kinase . ^^^ LPA induced ERK1 / 2 activation occurs predominantly through EGF R transactivation by Gi / Src and partly through activation of protein kinase C , which acts downstream of EGF R and Ras . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The stimulatory effect of aldosterone on ACE mRNA expression was completely blocked by a protein tyrosine kinase inhibitor ( genistein ) and JAK 2 inhibitor ( AG 490 ) , partially by Src kinase inhibitor ( PP 2 ) and epidermal growth factor receptor kinase inhibitor ( AG 1478 ) , but not by platelet derived growth factor receptor kinase inhibitor ( AG 1296 ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Zn2+ exposure induces phosphorylation of the tyrosine kinases , including Src and EGF receptor ( EGFR ) , and the p 38 mitogen activated protein kinase . ^^^ Inhibition of p 38 , Src , and EGFR kinases with pharmacological inhibitors markedly reduces Akt phosphorylation induced by Zn2+ . ^^^ However , the PI3K inhibitors do not show inhibitory effects on p 38 , Src , and EGFR . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The gastric mucin secretory responses to isoproterenol , furthermore , were inhibited by PP 2 , a selective inhibitor of tyrosine kinase Src responsible for ligand independent EGFR autophosphorylation , but not by ERK inhibitor , PD 98059 . ^^^ The findings underline the role of EGFR as a convergence point in gastric mucin secretion triggered by beta adrenergic GPCR activation , and demonstrate the requirement for Src kinase in EGFR transactivation . . ^^^ Gastric mucin secretion in response to beta adrenergic G protein coupled receptor activation is mediated by SRC kinase dependent epidermal growth factor receptor transactivation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Mechanistically , the activation of the PI3K / Akt pathway in keratinocyte differentiation depends on the activity of the epidermal growth factor receptor and Src families of tyrosine kinases and the engagement of E cadherin mediated adhesion . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Our results provide evidence for a putative pathway by which alpha ( 2 ) ARs activate MAPK and Akt in PC 12 cells , involving stimulation of PLC , AA release , AA metabolism by cytochrome P 450 dependent epoxygenase , stimulation of matrix metalloproteinases and subtype specific transactivation of EGFR through src activation and heparin binding EGF like growth factor release . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Each of these residues is targeted by one or more specific kinases : Y 142 by Fyn , Fer and cMet ; Y 489 by Abl ; and Y 654 by Src and the epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Rapid advances in cancer molecular genetics have identified numerous potential drug targets associated with abnormal control of cell division either downstream of the ErbBs , for example Ras and MEK , or in erbB associated signalling networks , like Src kinase , which affect the tumour cell motility and invasiveness . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We previously found that EGF ( epidermal growth factor ) increases the EGFR ( EGF receptor ) kinase binding affinity towards the major tyrosine phosphorylation sites in downstream adaptor proteins such as Gab 1 ( Grb 2 associated binding protein 1 ) and Shc [ Src homology 2 ( SH 2 ) domain and collagen containing protein ] , but not that towards EGFR autophosphorylation sites [ Fan , Wong , Deb and Johnson ( 2004 ) J . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Separate pathways mediate gastrointestinal peptide stimulation of additional tyrosine kinase pathways including transactivation of Src and epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These kinases are receptor kinases , which are transmembrane proteins such as epidermal growth factor receptor or cytoplasmic kinases such as Src kinase . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Both the PI3K / Akt and p 38 MAPK pathways are activated in a Src family kinase dependent fashion on EGF R activation and are important for EGF mediated VEGF production in pancreatic cancer cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Furthermore , the LPS induced suppression in gastric mucin synthesis was countered in a concentration dependent fashion by PD 153035 ( 81 . 7 % ) , a specific inhibitor of epidermal growth factor receptor ( EGFR ) kinase as well as PP 2 ( 69 . 8 % ) , a selective inhibitor of tyrosine kinase Src responsible for ligand independent EGFR transactivation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In addition to its estrogenic and / or antiestrogenic activities , genistein has been reported to inhibit steroidogenesis and block several protein tyrosine kinases , including epidermal growth factor receptor and src tyrosine kinases . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
This activation involves Src , intracellular Ca ( 2+ ) concentration ( [ Ca ( 2+ ) ] ( 1 ) ) elevation , reactive oxygen species ( ROS ) generation , and EGF receptor ( EGFR ) transactivation . ^^^ ERK1 / 2 potentiation by ouabain ( EC ( 50 ) approximately 100 muM ) involves PKC , Src , and alterations in [ Ca ( 2+ ) ] ( 1 ) but not ROS generation or EGFR transactivation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Here we use protein microarrays comprising virtually every Src homology 2 ( SH 2 ) and phosphotyrosine binding ( PTB ) domain encoded in the human genome to measure the equilibrium dissociation constant of each domain for 61 peptides representing physiological sites of tyrosine phosphorylation on the four ErbB receptors . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In contrast , the inhibition of Src but not MAPK prevented ErbB FAK induced chemotaxis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Here , we show that , through EGF receptor ( EGFR ) and erb B 2 , EGF induces tyrosine phosphorylation of ER preassociated with AR , thereby triggering the assembly of ER / AR with Src and EGFR . ^^^ In turn , estradiol and androgen antagonists , through the Src associated receptors , prevent Src activation by EGF and heavily reduce EGFR tyrosine phosphorylation and the subsequent multiple effects , including DNA synthesis and cytoskeletal changes in MCF 7 cells . ^^^ EGFR tyrosine phosphorylation , depending on Src , is a part of this mechanism . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In PC 12 cells , the EGF receptor ( EGFR ) is constitutively concentrated in lipid rafts , and further accumulation takes place upon EGF stimulation , followed by activation of SFKs , especially Src and Yes . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Since tumours exhibiting elevated EGFR signalling may possess elevated levels of Src activity , we wished to investigate the role of Src in our MCF 7 model of endocrine resistance . ^^^ The use of Src inhibitors in conjunction with EGFR inhibitors such as gefitinib may provide an effective method with which to prevent cancer progression and metastasis . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Moreover , inhibition of Src attenuated ERK1 / 2 responses by Phe , but not by HB EGF and EGF , indicating that Src acts upstream of the EGF R . ^^^ These data suggest that activation of the alpha 1 AR causes phosphorylation of ERK1 / 2 through activation of PKC , ROS and Src , and shedding of HB EGF , which binds to and activates the EGF R . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
H2O2 induced ERK activation was inhibited by the Src family selective inhibitor PP 2 and the epidermal growth factor receptor inhibitor AG 1478 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
HRS was found to sequester PELP 1 in the cytoplasm , leading to the activation of MAPK in a manner that is dependent on the epidermal growth factor receptor but independent of the estrogen receptor , Shc , and Src . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Thus , the positive regulation of E cadherin adhesion provided by Apc+ in vivo allows proper negative regulation of Egfr , Src , Pyk 2 , and MAPK , as well as RhoA activities . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : Using immunohistochemistry and image analysis , we quantified the levels of phospho Stat 3 ( pY Stat 3 ) , phospho Src ( pY Src ) , epidermal growth factor receptor , HER2 / neu , Ki 67 , estrogen receptor , Bcl 2 , Bcl xL , Survivin , and apoptosis in formalin fixed , paraffin embedded sections from invasive carcinomas and their paired nonneoplastic parenchyma . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor exposed to oxidative stress undergoes Src and caveolin 1 dependent perinuclear trafficking . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Specific epidermal growth factor receptor ( EGFR ) inhibitor AG 1478 and specific Src inhibitor PP 2 inhibited IR induced ERK1 / 2 activation but phosphatidylinositol 3 kinase inhibitor wortmannin did not . ^^^ IR caused EGFR tyrosine phosphorylation , whereas it did not induce EGFR autophosphorylation at Tyr 992 , Tyr 1045 , and Tyr 1068 or Src dependent EGFR phosphorylation at Tyr 845 . ^^^ These data suggest that IR induced ERK1 / 2 activation involves EGFR through a Src dependent pathway that is distinct from EGFR ligand activation . . ^^^ Src tyrosine kinase inhibitor PP 2 suppresses ERK1 / 2 activation and epidermal growth factor receptor transactivation by 10 irradiation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The effects of P 25 on matrix assembly and beta 1 integrin activation were inhibited by pretreatment with EGFR or Src kinase inhibitors , suggesting a role for both Src and EGFR in integrin activation by uPAR . ^^^ Phosphorylation of EGFR in response to P 25 occurred on Tyr 845 , an Src dependent phosphorylation site and was inhibited by PP 2 , the Src kinase inhibitor , consistent with Src kinase lying upstream of EGFR and integrin activation . ^^^ Cells null for Src kinases also showed a loss of P 25 induced matrix assembly , integrin activation , and EGFR phosphorylation . ^^^ These data provide evidence for a novel pathway of fibronectin matrix assembly through the uPAR dependent sequential activation of Src kinase , EGFR , and beta 1 integrin . . ^^^ Urokinase type plasminogen activator receptor regulates a novel pathway of fibronectin matrix assembly requiring Src dependent transactivation of epidermal growth factor receptor . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Both Src and ERK1 / 2 were phosphorylated in response to integrin aggregation , and blocking Src kinase activity completely abrogated ERK1 / 2 activation and uPA induction , whereas inhibition of epidermal growth factor receptor tyrosine kinase activity did not alter uPA expression . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
METHODS : Using parental and 5 src or c H ras transfected HAG 1 human gallbladder adenocarcinoma cell lines , effects of gefitinib on cytotoxicity , cell cycle purtubation and apoptosis , and tyrosine phosphorylation of EGFR , Akt , and Erk were determined by WST 1 assay , flow cytometry , and Western blots , respectively . ^^^ By contrast , gefinitib failed to inhibit the activation of both Akt and Erk in 5 src transfected cells and Erk , but not Akt in c H ras transfected cells , despite the blockade of EGFR activation in these respective cell lines . ^^^ CONCLUSION : Our results suggest that activated Ras and Src could induce gefitinib resistance by activating either or both of Akt and Erk signaling pathways , thus providing a strategic rationale for assessment of these specific signaling molecules downstream of EGFR to customize treatment . . ^^^ Activated Src and Ras induce gefitinib resistance by activation of signaling pathways downstream of epidermal growth factor receptor in human gallbladder adenocarcinoma cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The LHR mediated phosphorylation of the EGFR and Shc , the activation of Ras , and the phosphorylation of ERK1 / 2 are inhibited by expression of a dominant negative mutant of Fyn , a member of the Src family kinases ( SFKs ) expressed in MA 10 cells and by PP 2 , a pharmacological inhibitor of the SFKs . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
EGFR phosphorylation is increased in cells expressing Galphaq and this effect is inhibited by PP 2 , placing Src upstream of EGFR phosphorylation . ^^^ EGFR activation appears to be required for Galphaq mediated protection since inhibition of Src or EGFR rendered cells susceptible to 2DOG induced apoptosis . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) and Src tyrosine kinase cooperate in regulating EGFR mediated cell signaling and promoting cell transformation and tumorigenesis in pathological conditions . ^^^ Epidermal growth factor receptor ( EGFR ) and Src tyrosine kinase cooperate in regulating EGFR mediated cell signaling and promoting cell transformation and tumorigenesis in pathological conditions . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Overexpression of dominant negative PKCdelta or pretreatment with a PKCdelta inhibitor ( rottlerin ) or Src kinase family inhibitor ( PP 2 ) partially blocked LPA induced MMP activation , proHB EGF shedding , and EGFR tyrosine phosphorylation . ^^^ Down regulation of Lyn kinase , but not Src kinase , by specific small interfering RNA mitigated LPA induced MMP activation , proHB EGF shedding , and EGFR phosphorylation . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Nucleotide exchange stimulation by PE is prevented by PKC ( protein kinase C ) inhibition but not by EGFR [ EGF ( epidermal growth factor ) receptor ] blockade , despite the fact that EGFR inhibition aborts basal and PE induced Shc ( Src homology and collagen homology ) phosphorylation and Shc Grb 2 ( growth factor receptor bound protein 2 ) association . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Based on the importance of EGFR signaling in lung cancer , the known cooperation between EGFR and Src proteins , and evidence of elevated Src activity in human lung cancers , we evaluated the effectiveness of a novel orally bioavailable Src inhibitor dasatinib ( BMS 324825 ) in lung cancer cell lines with defined EGFR status . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In this study , we found that Abl kinases are constitutively activated , in highly invasive breast cancer cell lines , downstream of deregulated ErbB receptors and Src kinases . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
We show here that EGF R transactivation was sensitive to pertussis toxin ( PTX ) and phosphoinositide 3 kinase ( PI3K ) inhibitors and that it occurred independently from Src activity , despite the observation of a strong impairment of LTD 4 induced DNA synthesis following Src inhibition . ^^^ While PI3K and ROS involvement is an early event , the activation of Src occurs downstream of EGF R activation and is followed by the classical Ras ERK1 / 2 signaling pathway to control G 1 progression and cell proliferation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
PGE 2 stimulated phosphorylation of JNK in an EGF receptor dependent manner , and activation of the epidermal growth factor receptor required protein kinase C , src , and matrix metalloproteinase activities . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Inhibition of PKC and Src abolished the stimulatory effects of GnRH , but not that of EGF , consistent with a critical role of these signaling molecules upstream of the EGF R . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Neuregulin activates erbB 2 dependent src / FAK signaling and cytoskeletal remodeling in isolated adult rat cardiac myocytes . ^^^ We tested the hypothesis that erbB 2 signaling modulates focal adhesion formation via activation of a src / FAK pathway using adult rat ventricular myocytes in primary culture . ^^^ The erbB ligand neuregulin 1Beta ( NRG 1Beta ) induced phosphorylation of Src at Y 416 and Y 215 , and FAK at Y 861 . ^^^ Using antibody and pharmacological inhibitor strategies , we found that FAK activation was erbB 2 and Src dependent , but independent of PI 3 kinase / Akt pathway . ^^^ These effects of NRG 1Beta were prevented by a src inhibitor as well as an antibody to erbB 2 . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin dependent kinases ( CDKs ) . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
METHODS : SV 40 immortalized HCEC ( THCE ) monolayer was wounded and allowed to heal in the presence or absence of a selective inhibitor of the Src family kinases PP 2 and EGFR ligand heparin binding EGF like growth factor ( HB EGF ) . ^^^ Phosphorylation of extracellular signal regulated kinase ( ERK ) , AKT ( a major substrate of phosphatidylinositol 3 ' kinase [ PI3K ] ) , Src at tyrosine Y 416 , and EGFR at Y 845 was analyzed by Western blotting with antibodies specific to phosphorylated proteins . ^^^ CONCLUSIONS : These results suggest that Src kinase mediates wound induced EGFR transactivation and participates in a pathway to activate the PI3K AKT pathway downstream of EGFR in HCECs . . ^^^ SRC family tyrosine kinases in wound and ligand induced epidermal growth factor receptor activation in human corneal epithelial cells . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
In contrast , PAR 2 promoted Src activation and interaction of this kinase with EGFR . ^^^ In support of this , inhibition of Src kinase activity by PP 1 or siRNA blocked PAR 2 induced EGFR signaling cascade and cell growth . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
These findings demonstrate that the regulated phosphorylation of Cool 1 is necessary to maintain the balance between normal signalling by EGFR and Src versus aberrant growth and transformation . . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
The aim of the study was to test the hypothesis that expression of retinoid receptors ( RARalpha , RARbeta , RARgamma ) , rexinoid receptors ( RXRalpha , RXRbeta ) , thyroid hormone receptors ( TRalpha , TRbeta ) , estrogen receptors ( ERalpha , ERbeta ) , nuclear receptor coregulators ( N CoR , SRC 1 , SMRT ) , and in addition type 1 iodothyronine 5 ' deiodinase ( 5 ' DI ) , EGFR and erb B2 / neu would be different in mammary postlactating tissue in comparison with that of nonlactating mammary gland . ^^^ Using RT PCR , we have shown that expression of RARalpha , RXRalpha , TRalpha , ERalpha , ERbeta , N CoR , SRC 1 , SMRT and EGFR in rat was significantly increased in postlactating mammary gland when compared to that of nonlactating mammary tissue . ^^^
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P00533	Pubmed	SVM Score :0.0
NA