| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :1.2145268 |
| CD 28 induced tyrosine phosphorylation and PI 3 K activation was independent of p56lck protein tyrosine kinase ( PTK ) activity ( previously reported to be associated with CD 28 ) and was insensitive to inhibition by the PTK inhibitor herbimycin A . 1.2145268^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.77620809 |
| Under these conditions , CD 28 associates with activated lck and TCR zeta . 0.77620809^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Reimmunoprecipitation studies indicated that the cytoplasmic protein tyrosine kinases Lck and Fyn were associated with CD 28 . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| In this study , we demonstrate in coexpression studies that p56Lck and p59Fyn phosphorylate CD 28 primarily at Tyr 191 of the Tyr Met Asn Met motif , inducing a 3 to 8 fold increase in p 85 ( subunit of PI 3 kinase ) and GRB 2 SH 2 binding to CD 28 . ^^^ Further , ITK binding to CD 28 was dependent on the presence of p56Lck and is thus likely to act downstream of p56Lck / p59Fyn in a signaling cascade . p56Lck is therefore likely to be a central switch in T cell activation , with the dual function of regulating CD 28 mediated costimulation as well as TCR CD 3 CD4 signaling . . ^^^ Lck and p59Fyn regulate CD 28 binding to phosphatidylinositol 3 kinase , growth factor receptor bound protein GRB 2 , and T cell specific protein tyrosine kinase ITK : implications for T cell costimulation . ^^^ CD 28 interacts with three intracellular proteins phosphatidylinositol 3 kinase ( PI 3 kinase ) , T cell specific protein tyrosine kinase ITK ( formerly TSK or EMT ) , and the complex between growth factor receptor bound protein 2 and son of sevenless guanine nucleotide exchange protein ( GRB 2 SOS ) . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| A CD 28 induced , p56lck kinase independent pathway causes tyrosine phosphorylation of a 110 kDa substrate while recruitment of p56lck kinase activity is apparently required for CD 28 induced tyrosine phosphorylation of 97 and 68 kDa substrates as well as CD 28 induced increases in intracellular calcium . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Activation of src family kinase lck following CD 28 crosslinking in the Jurkat leukemic cell line . ^^^ Finally , lck could be found in anti CD 28 immunoprecipitates in exponentially growing Jurkat and in `` activated ' ' CD 28 ( i . e . , cross linked ) , but not in CD 28 in resting Jurkat cells . ^^^ Using the Jurkat leukemic cell line as a model , we have tested CD 28 crosslinking for its effects on the protein tyrosine kinases p56lck . ^^^ We report that following crosslinking of CD 28 , p56lck kinase activity is increased . ^^^ Crosslinking CD 28 causes a shift in the relative mobility of p56lck from 56 to 60 kD similar to that seen after crosslinking of CD 2 and CD 4 , cell surface receptors known to be associate with and activate p56lck . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Thus CD 28 signaling can activate src family kinases lck and fyn , as well as the Tec family kinase emt / itk . ^^^ Activation of extracellular signal regulated protein kinase ( ERK / MAP kinase ) following CD 28 cross linking : activation in cells lacking p56lck . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Functional LCK Is required for optimal CD 28 mediated activation of the TEC family tyrosine kinase EMT / ITK . ^^^ We have demonstrated that both the LCK and the EMT / ITK / TSK ( EMT ) intracellular tyrosine kinases are activated following cross linking of CD 28 . ^^^ Utilizing somatic cell mutants lacking LCK , we demonstrate that functional LCK is required for CD 28 induced activation of EMT as evidenced by increased tyrosine phosphorylation and kinase activity . ^^^ In support of a role for LCK in EMT activation , reconstitution of a LCK negative Jurkat T cell line by transfection with normal LCK recreates CD 28 mediated EMT activation . ^^^ In addition , increases in EMT association with CD 28 were eliminated in a LCK negative Jurkat cell line , but were restored following transfection of wild type LCK . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| In contrast , anti CD 28 monoclonal antibody stimulation led to in vitro phosphorylation of CD 28 on tyrosine that was manganese dependent and required Lck tyrosine kinase activity , as it was undetectable in J . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Analysis of CD 28 cytoplasmic tail tyrosine residues as regulators and substrates for the protein tyrosine kinases , EMT and LCK . ^^^ Early events in CD 28 signaling include recruitment and activation of phosphatidylinositol 3 kinase ( PI 3 kinase ) and activation of the protein tyrosine kinases ( PTKs ) , LCK and EMT . ^^^ To address this we studied the ability of truncation mutants and tyrosine to phenylalanine substitution mutants of the CD 28 cytoplasmic tail to activate LCK and EMT in Jurkat T leukemia cells . ^^^ Our results indicate that 1 ) activation of EMT is partially dependent upon tyrosine 173 of the CD 28 tail , although it does not require PI 3 kinase activation ; 2 ) activation of LCK is independent of CD 28 cytoplasmic tail tyrosine residues ; and 3 ) elements sufficient for the activation of both kinases are contained within the first half of the tail . ^^^ We demonstrate that EMT can phosphorylate all four tyrosines of the CD 28 tail , in contrast to LCK , which phosphorylates only tyrosine 173 . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| We demonstrate that following CD 28 ligation , a CD 28 associated tyrosine kinase activity is increased in parallel to activation of the T cell specific tyrosine kinase Itk ( Itk / Emt ) , while Lck and Fyn kinase activities are not increased . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Efficient CD 28 signalling leads to increases in the kinase activities of the TEC family tyrosine kinase EMT / ITK / TSK and the SRC family tyrosine kinase LCK . ^^^ Indeed , crosslinking of CD 28 increases the activity of the intracellular tyrosine kinases EMT / ITK and LCK . ^^^ We demonstrate herein that murine Y 170 ( equivalent to human Y 173 ) in CD 28 is also dispensable for activation of the SRC family tyrosine kinase LCK and the TEC family tyrosine kinase EMT / ITK . ^^^ In contrast , the distal three tyrosines in CD 28 are required for optimal IL 2 production as well as for optimal activation of the LCK and EMT / ITK tyrosine kinases . ^^^ Furthermore , PI3K is recruited to CD 28 in JCaM 1 cells which lack LCK and in which EMT / ITK is not activated by ligation of CD 28 . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| In contrast to the differential signaling of BW 828 and 9 . 3 in resting T cells , the two mAbs exhibited a similar pattern of early signaling events in activated T cells and Jurkat cells ( p 56 ( lck ) activation , association of phosphatidylinositol 3 kinase with CD 28 ) , indicating that the signaling capacity of CD 28 changes with activation . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Ligation of the TCR or CD 28 induces activation of phosphatidylinositol 3 kinase ( PI3K ) , the TEC family protein tyrosine kinase , EMT / ITK / TSK ( EMT ) , and the SRC family tyrosine kinase , LCK . ^^^ LCK is required for the activation and phosphorylation of EMT induced by ligation of the TCR or CD 28 placing LCK upstream of EMT in T cell signaling cascades . ^^^ In contrast , PI3K inhibitors did not alter CD 28 or CD 3 cross linking or LCK induced EMT phosphorylation . ^^^ CD 28 induced association of EMT with PI3K also requires functional expression of LCK . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| We investigated the role played by the protein tyrosine kinases Fyn , Lck , and ZAP 70 in these processes in a T cell hybridoma after physiological stimulation of the T cell receptor ( TCR ) and CD 28 . ^^^ Consistently , Vav was strongly phosphorylated in Lck deficient JCAM 1 cells after CD 28 ligation . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| In contrast , Lck induced phosphorylation of CD 28 resulted in the recruitment of phosphatidylinositol 3 kinase , but not SHP 2 . ^^^ These findings suggest that phosphorylation of CD 28 and CTLA 4 by Lck activates distinct intracellular signaling pathways . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Analysis of CD 3 and CD 28 induced signal transduction revealed a deficiency in signaling events that involved repressed tyrosine phosphorylation and enzymatic activities of a family of mitogen activated protein kinases , extracellular signal regulated kinase 2 , stress activated protein kinase / c jun N terminal kinase ( SAPK / JNK ) , and p38mapk , as well as p56lck and ZAP 70 in CBTCs compared with those in PBTCs . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Here , we show in heterologous COS 7 cells that co expression of Src family kinases such as Lck increases Tec activation or CD 28 mediated Tec activation , whereas co expression of kinase dead Lck blocks Tec activation or CD 28 mediated Tec activation . ^^^ Consistent with the hypothesis postulated above that Lck can regulate Tec activation , overexpression of kinase dead Lck can block Tec induced cytokine expression following CD 28 ligation . . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Synthetic peptides corresponding to the homologous regions found in CD 28 and FcepsilonRIbeta were also studied and comparable lck lyn binding potentials were detected . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| TCR alpha beta independent CD 28 signaling and costimulation require non CD 4 associated Lck . ^^^ The results demonstrate that constitutive levels of non CD 4 associated Lck functionally limit CD 28 mediated signaling . . ^^^ Whether the sequelae of signals generated through CD 28 either directly or in circumstances of costimulation require proximal events mediated by p56lck remains contentious . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Proline residues in CD 28 and the Src homology ( SH ) 3 domain of Lck are required for T cell costimulation . ^^^ Here we demonstrate that Lck and Fyn can be activated by proline motifs in the CD 28 and CD 2 proteins , respectively . ^^^ Supporting a role for Lck in CD 28 signaling , we demonstrate that CD 28 signaling in both transformed and primary T cells requires Lck as well as proline residues in CD 28 . ^^^ These data suggest that Lck plays an essential role in CD 28 costimulation . . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| MHC class 1 cross talk with CD 2 and CD 28 induces specific intracellular signalling and leads to growth retardation and apoptosis via a p 56 ( lck ) dependent mechanism . ^^^ In parallel experiments with the p 56 ( lck ) negative Jurkat mutant cell , JCaM1 . 6 , cross linking neither influenced cell signalling nor cellular growth functions , indicating a cardinal role of the src kinases in signal transduction via MHC 1 , CD 2 and CD 28 molecules . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| The Lck tyrosine kinase is involved in signaling by T cell surface receptors such as TCR / CD3 , CD 2 , and CD 28 . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| CD 28 and the tyrosine kinase lck stimulate mitogen activated protein kinase activity in T cells via inhibition of the small G protein Rap 1 . ^^^ The ability of CD 28 to stimulate Rap 1 GTPase activity was dependent on the tyrosine kinase Lck . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Signal transduction regions studied include the TCR zeta chain , the CD 4 coreceptor , the lck protein tyrosine kinase , and the CD 28 costimulatory receptor . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Lck plays a critical role in Ca ( 2+ ) mobilization and CD 28 costimulation in mature primary T cells . ^^^ We compared the phenotype and signaling capacity of Lck deficient T cells with T cells from mice expressing a dominant inhibitory form of Lck and found that both mouse strains have diminished numbers of mature CD 8 ( + ) T cells and respond poorly to CD 28 costimulation . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Inhibition of CD 28 mediated natural cytotoxicity by KIR2DL2 does not require p 56 ( lck ) in the NK cell line YT Indy . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Regulation of Lck activity by CD 4 and CD 28 in the immunological synapse . ^^^ Instead , the T cell accessory molecules CD 4 and CD 28 cooperated to induce autophosphorylation of Lck . ^^^ CD 4 recruited Lck to the T cell APC interface , whereas CD 28 sustained Lck activation . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Our evidence that the activation of Lck activates in T cells apoptotic pathways which are counteracted by Vav , a signaling molecule that cooperates with CD 28 to boost TCR signals , suggests a novel role for costimulation in protecting T cells from CD 4 mediated cell death . . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Stimulation of tyrosine phosphorylation and activation of ITK by the T cell antigen receptor , CD 28 and CD 2 requires the presence of the Src family kinase Lck in T cells . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Transgenic ( Tg ) overexpression of A 1 a in T cells via the lck distal promoter resulted in decreased apoptosis following activation either with concanavalin A or with antibodies to CD 3 and CD 28 and led to a doubling of T cell yield by 5 days . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| We synthesized chimeric receptors consisting of the extracellular and transmembrane domains of the class 1 MHC H 2K ( b ) molecule linked to the signaling domains of either TCR zeta , CD 28 and zeta , or CD 28 , zeta , and lck . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| This could be a result of a common mechanism involving perturbation in the formation of the central supramolecular activation cluster of the immunological synapse by impaired recruitment of CD 4 and CD 28 , thereby resulting in severely reduced lck activation . . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| The protein tyrosine kinases p 56 ( lck ) and the transmembrane tyrosine phosphatase CD 45 were all found to be involved in TCR CD 28 PGE ( 2 ) directed increase in HTLV 1 LTR activity . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| In this study , four colour flow cytometry was applied to study the surface bound molecules TCRalphabeta , CD 28 , CD 152 and CD 154 involved in T cell signalling and the signal transduction molecules CD3zeta , p56lck , p59fyn , ZAP 70 and phosphatidyl inositol 3 kinase ( PI 3 k ) as well as the intracellular cytokines interferon gamma ( IFN gamma ) , interleukin ( IL ) 4 and IL 2 as a functional read out of non stimulated and superantigen ( staphylococcus enterotoxin B ) stimulated blood T cells of multiple myeloma ( MM ) patients at different stages of the disease . ^^^ There was a marked reduction , particular in advanced stage MM , in the proportion of CD 4 and CD 8 cells expressing CD 28 , CD 152 , CD3zeta , p56lck , ZAP 70 and PI 3 k . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Studies with Jurkat cells deficient in Lck and CD 45 demonstrate that movement of CD 28 into lipid rafts does not require Lck and CD 45 and can occur despite reduction of CD 28 tyrosine phosphorylation to below the levels of detection . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Multiple modes of interaction between Lck and CD 28 . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| Here , molecular mapping of CD 28 costimulation showed that T ( reg ) cell generation requires a motif that binds the tyrosine kinase Lck , precisely the same motif that is required for CD 28 costimulation of interleukin 2 production . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| CD 28 and lipid rafts coordinate recruitment of Lck to the immunological synapse of human T lymphocytes . ^^^ Using CD 4 or CD 28 deficient murine T cells , it was suggested that recruitment of Lck to the IS depends on CD 4 , whereas CD 28 sustains Lck activation . ^^^ Thus , we performed a series of experiments to determine 1 ) whether Lck is recruited to the IS through lipid rafts ; and 2 ) whether Lck recruitment to the IS of human resting T cells depends on CD 4 or on CD 28 engagement . ^^^ We found that CD 28 , but not CD 4 , stimulation induced recruitment of Lck into detergent resistant domains as well as its accumulation at the IS . ^^^ We also found that Lck recruitment to the IS depends on the CD 28 COOH terminal PxxPP motif . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| RIfS curves were obtained for the Jurkat derivative JCaM 1 . 6 ( which lacks the key signaling protein Lck ) , cells preincubated with cytochalasin D ( an inhibitor of actin polymerization ) , and for surfaces functionalized with an antibody directed against the coreceptor CD 28 . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| HIV 1 transgenic rat CD4+ T cells develop decreased CD 28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation . ^^^ Here we identify abnormalities in activated HIV 1 Tg rat CD4+ T cells that include decreased pY 505 dephosphorylation of Lck ( required for Lck activation ) , decreased CD 28 function , reduced expression of the anti apoptotic molecule Bcl xL , decreased secretion of the mitogenic lympokine interleukin 2 ( IL 2 ) and increased activation induced apoptosis . ^^^ |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|