| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Candidate kinases include p56Lck , p59Fyn , zeta chain associated 70 kDa protein ( ZAP 70 ) , and ITK . ^^^ 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 ) . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| A synthetic peptide based on this site has been demonstrated to be a good in vitro substrate for ZAP 70 and a poor substrate for the T cell PTKs Lck and Itk . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Mice lacking Itk , a T cell specific protein tyrosine kinase , have reduced numbers of T cells and reduced responses to allogeneic major histocompatibility molecules . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity . ^^^ We found that Itk is tyrosine phosphorylated after TCR cross linking and that this phosphorylation depends on the presence of functional Lck . ^^^ To determine if this Lck dependence results from direct phosphorylation of Itk by Lck , we generated recombinant Itk and Lck using a baculovirus expression system and used these proteins in subsequent biochemical analyses . ^^^ We found that Lck phosphorylates Itk upon co expression in insect cells and , further , that this phosphorylation of Itk results in increased Itk in vitro kinase activity . ^^^ The major site of Lck phosphorylation on Itk was mapped to the conserved tyrosine ( Tyr 511 ) in the activation loop of the Itk kinase domain . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Tip is phosphorylated on tyrosine in cell free systems containing Lck , indicating that the viral protein is a substrate for this T cell specific kinase . ^^^ The product of the Herpesvirus saimiri open reading frame 1 ( tip ) interacts with T cell specific kinase p56lck in transformed cells . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy . ^^^ The role played in these phenomena by Lck and Itk , two protein tyrosine kinases essential for T cell signaling , was examined . ^^^ Early T cell responses ( membrane ruffling , Ca ( 2+ ) response , APC T cell adhesion ) were monitored in T cells overexpressing kinase defective ( KD ) Lck and Itk mutants by combining fluorescence imaging and electron microscopy . ^^^ Neither Lck nor Itk appears to be involved in the Ag independent formation of a small and labile contact interface between T cells and APCS : By contrast , the Ag induced Ca ( 2+ ) response in a cell population is similarly blunted in both KD transfectants . ^^^ The major effect of Lck KD is to reduce the probability of giving rise to quasi normal Ca ( 2+ ) responses , whereas overexpression of Itk KD results in a tuning down of all single cell Ca ( 2+ ) responses . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Analysis of in vitro kinase reactions with a panel of recombinant glutathione S transferase ( GST ) fusion tyrosine kinases ( Itk , Lck , ZAP 70 and Jak 3 ) revealed that only GST Itk efficiently phosphorylated a recombinant GST Rch1alpha fusion . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Biochemically , Itk is directly phosphorylated and activated by Lck . ^^^ |
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| Interacting proteins: Q08881 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 . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| This stimulation of tyrosine phosphorylation and activation of ITK can be mimicked by the Src family kinase Lck . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| To address the question of how these members of different families of PTKs functionally contribute to T cell development and to T cell activation , mice deficient for both Itk and either Lck or Fyn were generated . ^^^ The Itk / Lck doubly deficient mice exhibited a phenotype similar to that of Lck deficient mice . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Itk , a Tec family tyrosine kinase , acts downstream of Lck and phosphatidylinositol 3 ' kinase to facilitate T cell receptor ( TCR ) dependent calcium influxes and increases in extracellular regulated kinase activity . ^^^ First , the inositide binding pocket of the Itk pleckstrin homology domain directs the constitutive association of Itk with buoyant membranes that are the primary site of TCR activation and are enriched in both Lck and LAT . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Activation of PI 3 K and the src family kinase Lck , via stimulation of the CD 4 co receptor , can initiate beta 1 integrin activation that is dependent on Itk function . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Nonreceptor protein tyrosine kinases including Lck , ZAP 70 , and Itk play essential roles in T cell receptor ( TCR ) signaling . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Lyn , Lck , Syk , ZAP 70 , Btk , Itk and JAK ) is the earliest detectable signaling response upon activation of immune receptors ( T cell receptor , B cell receptor and FCepsilonR 1 ) , cytokine receptors and chemokine receptors in inflammatory cells . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| The EMT / ITK / TSK ( EMT ) tyrosine kinase is activated during TCR signaling : LCK is required for optimal activation of EMT . ^^^ EMT activation , as evidenced by increased EMT tyrosine phosphorylation and EMT associated kinase activity , was also greatly reduced following stimulation of the TCR in the JCaM1 . 6 Jurkat T cell mutants that lack LCK . ^^^ In support of a role for LCK in EMT activation , reconstitution of the LCK negative Jurkat T cell line by enforced expression of LCK restored TCR mediated EMT activation . ^^^ Taken together , the data indicate that the EMT tyrosine kinase is activated following cross linking of the TCR , a process in which LCK likely plays an important role . . ^^^ |
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| Interacting proteins: Q08881 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 . ^^^ Furthermore , this deletion reduces the ability of the Src family kinase Lck to activate ITK , as well as to induce the ITK mediated tyrosine phosphorylation of its substrate PLCgamma 1 . ^^^ By contrast , deletion of the SH 3 domain of ITK resulted in a two fold increase in the basal activity of ITK , and allowed this mutant to have an enhanced response to Lck . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of PLC gamma 1 is largely dependent on 3 kinds of protein tyrosine kinases ( PTKs ) , ie , Lck , ZAP 70 , and Itk . ^^^ We found that RosA efficiently inhibited TCR induced tyrosine phosphorylation and subsequent activation of Itk but did not inhibit Lck or ZAP 70 . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| CD 6 also associated with Lck , Fyn , and ZAP 70 , although at lower levels but additionally coprecipitated the Tec family kinase Itk , which is absent from CD 2 , CD 5 , and TCR complexes . ^^^ Lck together with Itk was the best combination of kinases , effectively phosphorylating synthetic peptides corresponding to a cytoplasmic sequence of CD 5 . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| We have shown previously that Itk is regulated by an activating transphosphorylation event in which Tyr 511 in the kinase domain is phosphorylated by Lck ( Heyeck , S . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| Lyn , Lck , Syk , ZAP 70 , Fyn , Btk , Itk ) is the earliest detectable signaling response upon antigen induced immunoreceptor activation in inflammatory cells . ^^^ |
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| Interacting proteins: Q08881 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 . ^^^ Furthermore , co transfection of LCK and EMT into COS 7 cells showed that EMT becomes phosphorylated in the presence of LCK . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| With the use of different Jurkat cell mutants it was demonstrated that CD 2 mediated activation of EMT required expression of LCK , but not require surface expression of the CD 3 zeta chain . ^^^ Receptor mediated activation of LCK does not in itself lead to activation of this Tec kinase since induction of LCK by ligation of CD 4 or CD 5 did not result in activation of EMT . ^^^ |
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| Interacting proteins: Q08881 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 . ^^^ |
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| Interacting proteins: Q08881 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 . ^^^ Further , inhibition of PI3K markedly decreased EMT in vitro autokinase activity induced by activated LCK . ^^^ 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 . ^^^ |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q08881 and P06239 |
Pubmed |
SVM Score :0.0 |
| NA |
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