| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.77005448 |
| The co stimulatory antigen CD 28 has been shown to bind to several intracellular proteins including phosphatidylinositol 3 kinase , growth factor receptor bound protein 2 ( Grb 2 ) , and ITK . 0.77005448^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| 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 ) . ^^^ 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 . . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| We have previously demonstrated that the TEC family tyrosine kinase EMT / ITK / TSK ( EMT ) is activated following cross linking of CD 28 . ^^^ However , although concurrent cross linking of the TCR and CD 28 results in a marked increase in production of the T cell growth factor IL 2 , it does not result in a significant alteration in the magnitude or duration of EMT activation . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
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 . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| CD 28 binds to several intracellular proteins including phosphatidylinositol 3 kinase ( Pl 3 kinase ) , the tyrosine kinase ITK and the growth factor receptor bound protein / Son of Sevenless ( GRB 2 / SOS ) complex . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
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 . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| Stimulation of surface CD 28 molecules on mast cells with anti CD 28 mAbs induced tyrosine phosphorylation of cellular proteins , including several protein tyrosine kinases and their substrates , such as Itk / Emt ( Emt ) , Btk , Syk , c Cbl , Shc , and Vav . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| Interleukin 2 ( IL 2 ) promoter activity stimulated by cross linking of CD 2 , TCR / CD3 , and CD 28 with antibodies was significantly reduced by transient expression of an Itk mutant lacking the kinase activity . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| Itk negatively regulates induction of T cell proliferation by CD 28 costimulation . ^^^ Itk , a nonreceptor protein tyrosine kinase specifically expressed in T cells and mast cells , has been implicated in the CD 28 signaling pathway because of reports that it becomes phosphorylated on tyrosines and associates with CD 28 upon cross linking of the cell surface molecule . ^^^ To determine whether Itk plays a functional role in CD 28 signaling , we compared T cells from Itk deficient mice and control mice for their responses to CD 28 costimulation . ^^^ Whereas the CD 3 mediated proliferative response was severely compromised in the absence of Itk , the calcineurin independent CD 28 mediated response was significantly elevated when compared with cells from control animals . ^^^ The results suggest that Itk has distinct roles in the CD 3 versus the CD 28 signaling pathways . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| The SH 3 domain of Itk / Emt binds to proline rich sequences in the cytoplasmic domain of the T cell costimulatory receptor CD 28 . ^^^ 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 . ^^^ We show that Itk forms an inducible complex with CD 28 , mediated by the SH 3 domain of Itk and the diproline motifs of CD 28 . ^^^ Site directed mutagenesis of the N terminal diproline motif of CD 28 abrogates the association of CD 28 with the SH 3 domain of Itk , while mutations within the C terminal diproline motif have little effect . ^^^ Peptides corresponding to the N terminal diproline motif were more efficient at abrogating the interaction between CD 28 and the SH 3 domain of Itk , than peptides corresponding to the C terminal diproline motif . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| One family member , ITK ( inducible T cell kinase ) , is involved in T cell activation and can be activated by the T cell receptor and the CD 28 cell surface receptor . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| Phosphatidylinositol 3 kinase is required for CD 28 but not CD 3 regulation of the TEC family tyrosine kinase EMT / ITK / TSK : functional and physical interaction of EMT with phosphatidylinositol 3 kinase . ^^^ 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 . ^^^ We report herein that inhibition of PI3K activity with the specific inhibitors LY 294002 and wortmannin markedly decreased EMT activation induced by CD 28 cross linking but not by CD 3 cross linking . ^^^ In contrast , PI3K inhibitors did not alter CD 28 or CD 3 cross linking or LCK induced EMT phosphorylation . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| Itk is expressed primarily in T cells and activated by TCR / CD3 , CD 28 , and CD 2 . ^^^ We also show that Tec can phosphorylate p 62 ( dok ) , one CD 28 specific substrate , whereas Itk can not . ^^^ Overexpression of Tec but not Itk can enhance the interleukin 2 promoter activity mediated by TCR / CD3 or CD 28 stimulation and introduction of a kinase dead Tec but not Itk can suppress interleukin 2 expression , indicating that Tec is directly involved in T cell activation . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| In addition , this association was enhanced following independent ligation of the CD 2 , CD 4 , or CD 28 costimulatory molecules , but not of CD 5 or CD 6 surface receptors , correlating to the induced tyrosine phosphorylation of Emt . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
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 . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| Itk is not essential for CD 28 signaling in naive T cells . ^^^ Early biochemical studies performed in tumor cell lines also implicated Itk in CD 28 signaling . ^^^ These data were complemented by functional studies on primary Itk / T cells that suggested a negative role for Itk in CD 28 signaling . ^^^ In this report , we describe a thorough analysis of CD 28 mediated responses in T cells lacking Itk . ^^^ Using purified naive CD4+ T cells from Itk / mice , we examine a range of responses dependent on CD 28 costimulation . ^^^ |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P10747 and Q08881 |
Pubmed |
SVM Score :0.0 |
| NA |
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