Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.57394148
We propose that the interaction of the p56lck SH 2 domain with zeta associated tyrosine phosphorylated ZAP 70 and / or Syk enables CD 4 to associate with antigen stimulated TCR / CD3 / zeta complexes . . 0.57394148^^^ We have previously shown that the p56lck SH 2 domain binds directly to tyrosine phosphorylated ZAP 70 . 0.5568755^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.53545036
Expression of the zeta chain is required for functional synergy of the T cell receptor with CD 4 in the activation of phospholipase C gamma 1 , which probably reflects an interaction between p56lck and zeta associated kinase ZAP 70 . 0.53545036^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.71088045
A phosphopeptide competing in vitro for the binding of tyrosine phosphorylated proteins to the SH 2 domain of p56lck specifically impedes the association of ZAP 70 with CD 8 alpha alpha / p56lck without affecting the zeta / ZAP 70 interaction . 0.71088045^^^ We have previously shown that the interaction of the p56lck SH 2 domain with zeta associated , tyrosine phosphorylated ZAP 70 and Syk kinases leads to an enhanced association of CD 4 with TCR / CD3 / zeta complex after CD 3 stimulation of Jurkat cells . 0.6373716^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.62442108
TCR / CD28 engagement induces the formation of endogenous Lck Dlgh 1 Zap70 Wiskott Aldrich syndrome protein ( WASp ) complexes in which Dlgh 1 acts to facilitate interactions of Lck with Zap 70 and WASp . 0.62442108^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Candidate kinases include p56Lck , p59Fyn , zeta chain associated 70 kDa protein ( ZAP 70 ) , and ITK . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Our results indicate that at least two kinases , lck and ZAP 70 , contribute to the CD 3 associated kinase activity . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Activated Lck phosphorylates T cell receptor zeta chains , which then recruit the ZAP 70 kinase to promote T cell activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We have previously shown that Lck plays a major role in the tyrosine phosphorylation of the TCR zeta chain and the ZAP 70 PTK . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Human immunodeficiency virus infection abolishes CD 4 dependent activation of ZAP 70 by inhibition of p56lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
CD 3 zeta ) , receptors on NK cells and their associated protein tyrosine kinases ( PTKs ; p56lck , p59fyn and ZAP 70 ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In vitro kinase assays revealed that Fyn and Lck , but not ZAP 70 , were capable of phosphorylating CasL . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
This process does not require the expression of tyrosine kinases Lck and Zap 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The SH 2 domains of ZAP 70 , SHP 1 and PLC gamma 1 and the SH 3 domains of lck , vav and HS 1 did not bind to pp 85 90 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
TCR signaling alone was sufficient to induce localization of Cdc 42 GTP , and functional Lck and Zap 70 kinases were required . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
TCR CD 3 complex , Lck and ZAP 70 kinases , and CD 4 co receptor are constitutively partitioned into a subset of rafts . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The dipalmitoyl peptide appeared to inhibit the phosphorylation of ZAP 70 , Lck , and T cell antigen receptor zeta in Jurkat . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
SLAT reduced the association of ZAP 70 with TCR zeta and interfered with ZAP 70 but not Lck signaling . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Phosphorylation of cellular substrates included src family kinase , p 56 ( lck ) and syk family kinase , ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
CYLD physically interacted with active Lck and promoted recruitment of active Lck to its substrate , Zap 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
NA
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Intracellular signaling from the T cell receptor ( TCR ) zeta / CD3 complex is likely to be mediated by associated protein tyrosine kinases such as p59fyn ( T ) , ZAP 70 , and the CD 4 : p56lck and CD 8 : p56lck coreceptors . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Recombinant SH 2 domains of Lck , Zap 70 , and Shc were tested in Ramos B cell lysates for phosphotyrosine dependent protein binding . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The phosphorylation of ZAP 70 and syk was enhanced markedly by overexpression of wild type lck but not by a kinase inactive mutant , suggesting that early Fc gamma R initiated activation of lck results in the subsequent regulation of syk family PTKs . ^^^ The regulatory interplay between src and syk family PTKs was emphasized further by the observation that lck overexpression enhanced the association of ZAP 70 with the zeta chain of the Fc gamma R complex . ^^^ Interestingly , the regulatory effects of lck on ZAP 70 , syk , and PLC gamma 2 could not be replaced by overexpression of either fyn or src , demonstrating a selective role for lck in effectively coupling Fc gamma R stimulation to critical downstream signaling events . ^^^ Taken together , our results suggest not only that Fc gamma R stimulation on NK cells is coupled to the intracellular activation of both ZAP 70 and syk , but that the src family member , lck , can selectively regulate this tyrosine kinase cascade . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We show here that CD 59 cross linking induces a time dependent activation of p56lck and of p70zap ( ZAP 70 ) in CD 3 positive Jurkat cells , leading to the stimulation of the T cell receptor zeta / ZAP 70 signaling cascade and interleukin 2 ( IL 2 ) synthesis . ^^^ In contrast , only activation of CD 59 associated p56lck occurs in CD 3 negative Jurkat cells , while IL 2 production is impaired , consistent with the lack of ZAP 70 tyrosine phosphorylation observed in these cells . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
T TIL expressed normal levels of CD 3 epsilon , TCR zeta chain , and the three tyrosine kinases , p56lck ( Lck ) , p59fyn , and ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
When expressed in COS cells , Y493F mutated ZAP 70 demonstrated normal basal kinase activity , but , unlike wild type ZAP 70 , could not be activated by tyrosine phosphorylation induced by incubation with pervanadate or by co expression of constitutively activated Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The earliest event detected in the sensitive cell line was a dramatic increase in the tyrosine phosphorylation of an 85 , 000 M ( r ) protein ( p 85 ; 30 s ) , followed by mobility shifts of raf 1 , mitogen activated protein kinase kinase ( MEK ) , mitogen activated protein ( MAP ) kinase , lck and ZAP 70 ( within 5 min ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In addition , autophosphorylation of ZAP 70 when bound to zeta or eta resulted in the generation of multiple distinct ZAP 70 phosphorylated tyrosine residues which had the capacity to bind the SH 2 domains of fyn , lck , GAP , and abl . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The activity of baculoviral expressed ZAP 70 was up regulated 10 fold when ZAP 70 was co infected and phosphorylated by the src family PTK , lck . ^^^ Mutation of Y 493 alone abrogated the ability of ZAP 70 to be activated by lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Here , we show that the transmembrane form of CD 16 transfected in a CD 3 Jurkat cell line associates with p56lck and ZAP 70 PTKs . ^^^ Comparative studies demonstrate that similar to zeta , MB 1 protein of the IgM receptor also binds to p56lck and ZAP 70 in T cells and induces strong activation responses , whereas CD 3 gamma , delta and epsilon chains do not interact with ZAP 70 and transduce weak signals . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
At least three nonreceptor tyrosine kinases have been implicated in this signaling cascade : p59fyn ( T ) , p56lck , and ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
By analyzing derivatives containing an activated version of either p56lck or p59fynT , it was observed that the two Src related enzymes augmented T cell receptor ( TCR ) mediated tyrosine phosphorylation of Zap 70 , as well as its association with components of the antigen receptor complex . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Since tyrosine phosphorylated pp29 / 30 selectively interacts with the Src homology type 2 domains ( SHZ ) of the protein tyrosine kinases p56lck and p59fyn but not ZAP 70 the present data suggest that pp29 / 30 represents a novel signaling receptor associated phosphoprotein likely involved in the activation of human T lymphocytes and NK cells . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Both the src family tyrosine protein kinases Lck , Fyn , Lyn and Blk and the syk family tyrosine protein kinases Syk and ZAP 70 play a role in lymphocyte activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We applied this technique to the analysis of in vitro sites of tyrosine phosphorylation induced on the T cell specific protein tyrosine kinase ZAP 70 in the absence and presence of p56lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
These studies are consistent with the concept that augmentation of [ Ca2+ ] 1 by stimulated T cell receptors requires activation of a kinase , probably a tyrosine kinase such as p56lck , ZAP 70 or p59fyn , and is independent of PKC . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Recent biochemical and genetic evidence has implicated at least three cytoplasmic protein tyrosine kinases ( PTKs ) , Lck , Fyn , and ZAP 70 , that are involved in the initiation of TCR signal transduction . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Anti TCR / CD3 stimulation of the TCR / CD3+ J 32 3 . 2 cells resulted in a weak stimulation of both the phosphatidyl inositol and tyrosine kinase signal transduction pathways , as measured by changes in the level of free intracellular calcium , tyrosine phosphorylation of TCR zeta , CD 3 epsilon and ZAP 70 , p56lck , or p59fyn tyrosine kinase activity and IL 2 gene activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Three nonreceptor tyrosine kinases , p56lck , p60fyn , and ZAP 70 , are known to be involved in T cell receptor ( TCR ) signaling , albeit their functional roles appear to be different . ^^^ Whereas p60fyn and ZAP 70 are functionally associated with the T cell antigen receptor , p56lck is essential for TCR signaling without being directly coupled to the TCR . ^^^ We have studied a mutant variant of the Jurkat T cell line ( J 32 3 . 2 ) , in which basal activities of p56lck and p60fyn are 2 to 2 . 5 fold reduced relative to those in its parental line ( J 32 ) while basal activity of ZAP 70 remains unchanged , and compared responses of J 32 3 . 2 and J 32 to TCR stimulation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
ZAP 70 kinase . p56lck , a member of the src family of protein tyrosine kinases , is an essential component in T cell receptor ( TCR ) signal transduction . p56lck contains a src homology 2 ( SH 2 ) domain found in a number of proteins involved in intracellular signaling . ^^^ Evidence suggests that binding of ZAP 70 to p56lck SH 2 is direct and not mediated by zeta . ^^^ The significance of this interaction was further investigated in vivo . p56lck could be coprecipitated with the zeta / ZAP 70 complex and conversely , ZAP 70 was detected in p56lck immunoprecipitates of activated Jurkat cells . ^^^ The physical association of p56lck and ZAP 70 during activation supports the recently proposed functional cooperation of these two tyrosine kinases in TCR signaling . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In addition , whereas T cell stimulation results in down regulation of Lck , no significant change in ZAP 70 or Syk protein is detected . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Cytoplasmic tyrosine residues in Ig beta were required for recruitment and activation of ZAP 70 , but these amino acids were not essential for the activation of Fyn and Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Finally , using a heterologous system , it was demonstrated that the ability of Zap 70 to cause tyrosine phosphorylation of p120c cbl was dependent on Lck or FynT mediated signals . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
This compound is a nanomolar inhibitor of Lck and FynT , inhibits anti CD 3 induced protein tyrosine kinase activity in T cells , demonstrates selectivity for Lck and FynT over ZAP 70 , and preferentially inhibits T cell receptor dependent anti CD 3 induced T cell proliferation over non T cell receptor dependent phorbol 12 myristate 13 acetate / interleukin 2 ( IL 2 ) induced T cell proliferation . ^^^ This compound offers a useful new tool for examining the role of the Lck and FynT tyrosine kinases versus ZAP 70 in T cell activation as well as the role of other Src family kinases in receptor function . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Third , the recruitment of ZAP 70 to the TCR / CD3 complex was seen only in animals with an increase in in vitro p56lck kinase activity after T cell activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Further analysis indicated that the SH 2 domain of Lck can directly recognize both ZAP 70 and zeta in immunoprecipitates from TCR stimulated cells . ^^^ Our findings demonstrate that the SH 2 domain of Lck is essential for the initiation of signaling events following TCR stimulation probably as a result of its ability to mediate an interaction between Lck and the ZAP 70 tyrosine kinase and / or the zeta subunit of the T cell receptor . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Hematopoietic cell phosphatase ( HCP ) regulates p56LCK phosphorylation and ZAP 70 binding to T cell receptor zeta chain . ^^^ Ligation of the T cell receptor complex and CD 4 leads to activation of the protein tyrosine kinases p56lck and p59fyn resulting in phosphorylation of TcR zeta chain and the recruitment of ZAP 70 . ^^^ In this study , we have reconstituted p56lck phosphorylation of TcR zeta and ZAP 70 recruitment in heterologous cells and examined the role of the tyrosine phosphatase HCP in regulating the process . ^^^ HCP dephosphorylated p56lck , ZAP 70 and the TcR zeta chain . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
TCR activation of ZAP 70 is impaired in CD4+CD8+ thymocytes as a consequence of intrathymic interactions that diminish available p56lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The T cell receptor specific kinases FYN , LCK , and ZAP 70 as well as the RAS pathway were found to be activated in T cells of Ctla 4 / mutant mice . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Lck regulates the tyrosine phosphorylation of the T cell receptor subunits and ZAP 70 in murine thymocytes . ^^^ Moreover , ligation of the TCR expressed on thymocytes from Lck deficient mice largely failed to induce the phosphorylation of TCR zeta , CD 3 epsilon , or ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Several tyrosine kinases have been detected associated to the CD 3 TcR complex in stimulated or unstimulated cells , including p56lck , p59fyn and ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Binding affinities of the SH 2 domains of ZAP 70 , p56lck and Shc to the zeta chain ITAMs of the T cell receptor determined by surface plasmon resonance . ^^^ Recent evidence suggests that the zeta chains provide docking space for several key signal transduction molecules such as ZAP 70 , p56lck , and Shc . ^^^ To determine if ZAP 70 , p56lck , and Shc bind to particular zeta chain ITAM sequences , quantitative free solution measurements of binding affinities ( Kd ) were obtained by use of surface plasmon resonance technology . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In contrast to the T cell protein tyrosine kinase , Lck , ZAP 70 did not phosphorylate the cytoplasmic portion of the TCRzeta chain or short peptides corresponding to the CD3epsilon or the TCRzeta immunoreceptor tyrosine based activation motifs . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
These results are the first report where dual activation of the Lck and Fyn PTK does not result in normal downstream signaling through the ZAP PTK , We suggest by analogy to SCID resulting from ZAP 70 mutations , that the dissociation of upstream PTK activation from ZAP 70 signaling contributes to T cell depletion by HIV and to the development of AIDS . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The protein tyrosine kinase ( PTK ) Lck phosphorylates the zeta chain , which in turn associates with another PTK , ZAP 70 , and stimulates its phosphorylation activity . ^^^ Circular dichroic analysis reveals a random coil conformation . zeta , phosphorylated using recombinant Lck , associates with recombinant ZAP 70 tandem SH 2 domains . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We demonstrated that the protein tyrosine kinase ZAP 70 was recruited to the endosomal fraction upon CD 2 stimulation with kinetics similar to that of p 56 ( lck ) , suggesting that recruitment of protein tyrosine kinases to endosomal vesicles could promote specific transduction signals at the intracellular level . . ^^^ Recruitment of activated p56lck on endosomes of CD 2 triggered T cells , colocalization with ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Stimulation of the T cell antigen receptor CD 3 complex signaling pathway by the tyrosine phosphatase inhibitor pervanadate is mediated by inhibition of CD 45 : evidence for two interconnected Lck / Fyn or zap 70 dependent signaling pathways . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Triggering via Fc mu R also induced the activity of Syk and Zap 70 , tyrosine kinases demonstrated to associate with zeta and Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In addition , CD 28 mediated costimulation may prevent the induction of anergy by facilitating the effective association of TCR zeta and CD 3 epsilon with the critical protein tyrosine kinase lck , and the subsequent recruitment of ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The utility of the assay has been demonstrated in an examination of the ligand specificity of the SH 2 domains of the tyrosine kinases ZAP 70 , Syk , and Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
CD 94 stimulation of group A clones induced the rapid activation of intracellular protein tyrosine kinases ( i . e . , lck and ZAP 70 ) , phospholipase C , and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Total amounts of protein tyrosine kinases ( PTKs ) Lck , Fyn , and ZAP 70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic / AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection . ^^^ Unexpectedly , the detection of Lck , Fyn , and ZAP 70 was reversed after the treatment of cell lysates with dithiothreitol . ^^^ This suggests that PTKs Lck , Fyn , and ZAP 70 were modified by a mechanism altering the status of sulfhydryl groups . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We used the LacZ gene as the marker gene and the cytokine interleukin ( IL ) 7 or dominant negative ( dn ) forms of the T cell tyrosine kinases ZAP 70 and lck as genes of interest . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Several studies have suggested a model in which p56lck would be responsible after CD 3 triggering for the phosphorylation of particular tyrosine residues in the immunoreceptor tyrosine based activation motifs of the CD 3 chains , inducing the recruitment and the tyrosine phosphorylation of ZAP 70 . ^^^ Altogether , these findings suggest that CD 2 could bypass the PTK ZAP 70 for PLCgamma 1 activation and involves a preferential cascade comprising p56lck and a p 62 protein , possibly acting as an anchor molecule . . ^^^ The T cell specific protein tyrosine kinase ( PTK ) ZAP 70 is believed to play a key role in early tyrosine phosphorylations of cellular proteins induced by CD 3 stimulation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The kinase , SH 3 , and SH 2 domains of Lck play critical roles in T cell activation after ZAP 70 membrane localization . ^^^ Therefore , Lck functions in multiple manners in T cell activation for the steps following ZAP 70 binding to ITAM . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In this report , we demonstrate that specific inhibition of Lck expression in Th 2 cells , in the presence of normal levels of functional Fyn PTK , has profound consequences on multiple events following TCR stimulation , including an altered pattern of tyrosine phosphorylated substrates , defective phosphorylation of TCR zeta and ZAP 70 , defective Ca2+ mobilization , and a approximately 90 % reduction in proliferative responses to antigenic and mitogenic stimuli . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In the course of these experiments , we found that the Syk PTK , but not the ZAP 70 PTK , is able to mediate TCR signaling independently of CD 45 and of Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The protein tyrosine kinase ZAP 70 is implicated , together with the Src kinase p 56 ( lck ) , in controlling the early steps of the T cell antigen receptor ( TCR ) signaling cascade . ^^^ The ZAP 70 mutant studied here could be phosphorylated on tyrosine when associated to the TCR zeta chain and was able to bind p 56 ( lck ) . ^^^ This result demonstrates that Tyr 492 and Tyr 493 are not responsible for the Src homology domain 2 mediated association of p 56 ( lck ) with ZAP 70 . ^^^ Our data are most consistent with a model in which recruitment to the TCR allows ZAP 70 autophosphorylation and binding to p 56 ( lck ) , which in turn phosphorylates Tyr 492 and / or Tyr 493 with consequent up regulation of the ZAP 70 kinase activity . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
To study the role of ZAP 70 catalytic activity in this process , a substrate capable of distinguishing between the activities of ZAP 70 and other PTKs would be useful , especially since it has recently been shown that ZAP 70 interacts with another T cell PTK , Lck . ^^^ We have thus identified a site of phosphorylation on the cytoplasmic fragment of the erythrocyte band 3 protein that is recognized by ZAP 70 , but not Lck . ^^^ 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 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Upon CD 3 engagement , ZAP 70 was also found associated with the TCR complex and the kinase activity ( p 56 ( lck ) ) associated with CD 8 increased . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Localization of Zap 70 , the gene for a T cell specific protein tyrosine kinase , to mouse and rat chromosomes by fluorescence in situ hybridization and molecular genetic linkage analyses . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
T cell activation stimulates p 56 ( lck ) , p 59 ( fyn ) , ZAP 70 , Vav SLP 76 binding , and IL 2 transcription . ^^^ Therefore , while p 56 ( lck ) regulates proximal events , ZAP 70 acts downstream on targets such as SLP 76 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In late endosomes , the internalized TCR / CD3 complex was found to be associated with an active protein kinase , distinct from p 56 ( lck ) and p 59 ( fyn ) , which were mainly present in early endosomes , and ZAP 70 , which was only present in the postnuclear supernatant . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
MHC class 1 ligation of human T cells activates the ZAP 70 and p56lck tyrosine kinases , leads to an alternative phenotype of the TCR / CD3 zeta chain , and induces apoptosis . ^^^ Furthermore , we demonstrate that the p56lck tyrosine kinase is tyrosine phosphorylated following MHC 1 ligation , and that a p56lck negative Jurkat T cell mutant does not induce phosphorylation of the zeta chain and the ZAP 70 kinase following MHC 1 ligation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Major tyrosine phosphorylated proteins were identified by immunoblotting , and included p56lck , p59fyn , zeta associated protein tyrosine kinase of 70 , 000 MW ( ZAP 70 ) , mitogen activated protein ( MAP ) kinase , c Cb 1 , and phospholipase C gamma . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Aberrant TCR mediated signaling in CD 45 null thymocytes involves dysfunctional regulation of Lck , Fyn , TCR zeta , and ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Consistent with this observation , pp 55 selectively binds to isolated SH 2 domains of Lck , Lyn , Src , and Fyn but not to the SH 2 domains of ZAP 70 , Syk , Shc , SLP 76 , Grb 2 , phosphatidylinositol 3 kinase , and c abl in vitro . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
ZAP 70 becomes phosphorylated and activated by LCK protein tyrosine kinase after interaction of its two NH 2 terminal SH 2 domains with tyrosine phosphorylated subunits of the activated TCR . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Defective TCR stimulation in anergized type 2 T helper cells correlates with abrogated p 56 ( lck ) and ZAP 70 tyrosine kinase activities . ^^^ In contrast to untreated Th 2 cells , anergized Th 2 cells failed to respond to anti CD 3 mAb with either increased tyrosine kinase activity or increased levels of tyrosine phosphorylation of p 56 ( lck ) or ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
These data indicated that in Jurkat T cells , CD 38 receptor triggering results in Lck regulated activation of both Raf 1 / MAP kinase and CD 3 zeta / ZAP 70 / phospholipase C gamma 1 signaling pathways . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Transduction of TCR signals in the thymus involves tyrosine phosphorylation of the protein tyrosine kinase ZAP 70 by p 56 ( lck ) and results in induction of ZAP 70 enzymatic activity . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The aim of this study was two fold : first , to investigate the levels of CD3zeta , p 56 ( lck ) , p 59 ( fyn ) , ZAP 70 , protein kinase C alpha ( PKC alpha ) and phospholipase C gamma ( PLC gamma ) in MM PBT cells ; second , to determine whether levels of expression were correlated with clinical or prognostic factors . ^^^ On average , PKC alpha was the only significantly decreased ( P < 0 . 001 ) signalling molecule , whereas levels of CD3zeta , p 56 ( lck ) , p 59 ( fyn ) , PLC gamma and ZAP 70 were not statistically different . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
T cell antigen receptor ( TCR ) signalling has been shown to involve two classes of tyrosine protein kinases : the Src related kinases p 56 ( lck ) and p 59 ( fyr ) , and the Zap 70 / Syk family kinases . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The anergic T cells induced by immobilized IAS MBP ( 91 103 ) complex or anti TCR ( H 57 ) showed differential expression of lck ( 56 kDa ) and Zap 70 ( 70 kDa ) proteins . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Jak 3 was most sensitive to suppression by RCC S ; however , reduction in expression of p 56 ( lck ) , p 59 ( fyn ) , and ZAP 70 was observed in some experiments . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Singly S acylated LCK mutants , which were expressed in part at the plasma membrane , efficiently reconstituted the induced association of phospho zeta with ZAP 70 and intracellular Ca2+ fluxes triggered by the TCR . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Initial experiments in epithelial cells indicated that ZAP 70 is diffusely located throughout the quiescent cell , and accumulates at the plasma membrane upon cellular activation , a phenotype enhanced by the coexpression of Lck and the initiation of ZAP 70 kinase activity . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
It facilitates recruitment of SHP 1 phosphatase to TCR CD 3 complex and affects phosphorylation of Lck and ZAP 70 kinase , but not of CD 3 zeta chain upon TCR triggering . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
This coordinated disappearance takes place whenever the TCR is triggered , even when the coreceptor does not engage the cognate MHC molecule and is the consequence of binding of the coreceptor associated Lck to ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
By contrast , it is sufficient to induce the phosphorylation of tyrosine residues on p56lck , the TCR zeta chain as well as ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Second , the ITAM from YE Nef is phosphorylated on tyrosine residues by Lck and associates with ZAP 70 , a T cell specific tyrosine kinase . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Conversely , signal transduction through the TCR requires the tyrosine kinases Lck and ZAP 70 and the tyrosine phosphatase CD 45 . ^^^ Here we show that , unexpectedly , transmission of growth inhibitory signals by interferon alpha ( IFN alpha ) in T cells requires the expression and association of CD 45 , Lck and ZAP 70 with the IFN alpha receptor signalling complex . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In addition , CD 45 is reported to associate with several intracellular protein tyrosine kinases including p56lck and p59fyn of the src family , and ZAP 70 of the Syk family , and with numerous proteins of 29 34 kDa . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Signal transduction involves CD 3 zeta phosphorylation by Lck tyrosine kinase and activation of ZAP 70 which regulates signaling pathways through PKC , Ca++ and Ras / Raf kinase cascade . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In this study we analyze the contribution of p 56 ( lck ) , as well as the role of ZAP 70 , the second class of protein tyrosine kinase involved in T cell activation , in Sam 68 tyrosine phosphorylation in the human Jurkat T cell line . ^^^ Using the src inhibitor PP 1 [ 4 amino 5 ( 4 methylphenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyrymidine ] and cell variants with defective expression of p 56 ( lck ) or expressing a dominant negative form of ZAP 70 , we demonstrate that , while both p 56 ( lck ) and ZAP 70 are dispensable for the low constitutive phosphorylation of Sam 68 observed in Jurkat cells , a cooperation between the two kinases is required to increase its rapid phosphorylation observed in vivo after CD 3 stimulation . ^^^ We also show that recombinant forms of both p 56 ( lck ) and ZAP 70 phosphorylate Sam 68 in vitro . ^^^ We conclude that p 59 ( fyn ) and p 56 ( lck ) differently participate in regulating the phosphorylation state of Sam 68 in T cells and that ZAP 70 may contribute to Sam 68 tyrosine phosphorylation and to the specific recruitment of this molecule after CD 3 stimulation . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
T cell antigen receptor ( TCR ) engagement activates multiple protein tyrosine kinases ( PTKs ) , including the Src family member , Lck , and the Syk related PTK , ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Thus , in these cells we observed increased phosphotransferase activity of Lck as well as constitutive tyrosine phosphorylation of the TCR associated ZAP 70 kinase and expression of the related Syk protein tyrosine kinase . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
All glycosylphospha tidylinositol ( GPI ) anchored proteins ( CD 14 , CD16B , CD 48 , CD 59 , CD 87 and GPI anchored versions of CD 2 and CD 25 ) and protein tyrosine kinase ( PTK ) Lck but not transmembrane proteins ( CD 2 , CD 4 , CD 5 , CD 6 , CD 8 ) and PTK ZAP 70 were in part localized in buoyant , lipid rich , detergent resistant membrane GPI microdomains of the COS cells . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Cross linking of the T cell antigen receptor ( TCR ) CD 3 complex induces rapid tyrosine phosphorylation and activation of Src ( Lck and Fyn ) and Syk ( Syk and Zap 70 ) family protein tyrosine kinases ( PTKs ) which , in turn , phosphorylate multiple intracellular substrates . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Genetic evidence of a role for Lck in T cell receptor function independent or downstream of ZAP 70 / Syk protein tyrosine kinases . ^^^ T cell antigen receptor ( TCR ) engagement results in sequential activation of the Src protein tyrosine kinases ( PTKs ) Lck and Fyn and the Syk PTKs , ZAP 70 and Syk . ^^^ The KS chimera and downstream ZAP 70 or Syk substrates , such as SLP 76 , were still phosphorylated when expressed in Lck deficient JCaM1 . 6 T cells . ^^^ However , expression of the KS chimera in JCaM1 . 6 cells failed to rescue downstream signaling events , demonstrating a functional role for Lck beyond the activation of the ZAP 70 and Syk PTKs . ^^^ These results indicate that downstream TCR signaling pathways may be differentially regulated by ZAP 70 and Lck PTKs and provide a mechanism by which effector functions may be selectively activated in response to TCR stimulation . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Here , we show that agonists cause association of active lck and active ZAP 70 with p 120 GTPase activating protein ( p 120 GAP ) . ^^^ In contrast , partial agonists do not activate lck or ZAP 70 , but induce association of p 120 GAP with inactive ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In addition , it was found that the in vitro kinase activities of the T cell receptor associated protein tyrosine kinase Lck ( p56Lck ) and ZAP 70 but not Fyn ( p59Fyn ) were lower in T cells from old rats than in T cells from young rats . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Although p59fyn and ZAP 70 protein tyrosine kinases were expressed at normal levels , a marked decrease in the level of p56lck was noted . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In particular , phosphorylation of ZAP 70 kinase in thymocytes was uncoupled from a requirement for CD 4 mediated Lck activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
TcRzeta / CD3 ligation initiates a signaling cascade involving CD4 / CD8 p 56 ( lck ) , p 59 ( fyn ) , and ZAP 70 , as well as lymphoid downstream proteins VAV , SLP 76 , and FYB / SLAP . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Although signaling pathways to discriminate these selections are largely unknown , ZAP 70 and Lck are important for both processes , whereas calcineurin and MAPK pathway play crucial roles in positive selection . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
With the engagement by either whole anti class 2 antibody or its Fab fragments , the enzymatic activity of p56lck and ZAP 70 increased , but there was no increase in p59fyn activity . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Roles of Lck , Syk and ZAP 70 tyrosine kinases in TCR mediated phosphorylation of the adapter protein Shc . ^^^ Moreover , co expression of Syk or ZAP 70 with Lck resulted in enhanced phosphorylation of Shc on all three sites , suggesting a synergy between the syk family and scr family kinases . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Upon removal of the PTP inhibitor , the tyrosine phosphorylated proteins , including Lck , Fyn , Syk , Zap 70 , and CD 35 zeta are rapidly dephosphorylated . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We also detected abnormally low levels of the signaling molecules T cell receptor ( TCR ) zeta , ZAP 70 and p56lck in 4 of 14 breast cancer patients , i . e . , defects in T cell signaling molecules . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We find that Txk exhibits a substrate preference in vitro quite distinct from that of the major T cell kinases Lck and ZAP 70 , suggesting that Tec family kinases might act on a distinct range of substrates . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
However , p 59 ( fyn ) immuno precipitates obtained from unstimulated peripheral blood SLE T cells showed enhanced PTK activity as compared to controls , whereas the PTK activity of p 56 ( lck ) and ZAP 70 molecules was comparable in both groups . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Expression of p 56 ( lck ) and Zap 70 , but not phospholipase C gamma 1 , was reduced in these patients ' T cells relative to those obtained from normal individuals . ^^^
Interacting proteins: P43403 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 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Endogenous CD 45 AP coimmunoprecipitated with Lck and ZAP 70 in both CD 45 positive T cells and their CD 45 negative variants after stimulation by antigen receptor ligation . ^^^ Concomitantly , CD 45 coimmunoprecipitated with Lck and ZAP 70 after T cell receptor mediated stimulation of CD 45 positive cells . ^^^ Recombinant CD 45 AP exhibited specific binding to Lck and ZAP 70 protein tyrosine kinases , but not to Fyn or Csk , in lysates of both CD 45 positive and negative T cells . ^^^ These results demonstrate that CD 45 AP associates directly and selectively with Lck and ZAP 70 in response to T cell receptor mediated stimulation . ^^^ The associations of CD 45 AP with Lck and ZAP 70 may mediate the functional interactions of these kinases with CD 45 during antigen receptor stimulation . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
This is accompanied by a particular pattern of inhibition of early tyrosine kinases , including Zap 70 and p 59 ( fyn ) inhibition , but not overall inhibition of p 56 ( lck ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In this report , we show that CTLA 4 can associate with the Src kinases Fyn and Lck and that transfection of Fyn or Lck , but not the unrelated kinase ZAP 70 , can induce tyrosine phosphorylation of CTLA 4 on residues Y 201 and Y 218 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In particular , ES 62 acts by modulating activation of the tyrosine kinases Fyn , Lck and ZAP 70 leading to selective disruption of TCR coupling to the phospholipase D , protein kinase C , phosphoinositide 3 kinase and RasMAPkinase signalling cascades . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The Src family kinase Lck is required for the initial events in TCR signaling , such as the phosphorylation of the TCR complex and the activation of ZAP 70 , but little is known of its role in downstream signaling . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Following T cell antigen receptor ( TCR ) engagement , the protein tyrosine kinase ( PTK ) ZAP 70 is rapidly phosphorylated on several tyrosine residues , presumably by two mechanisms : an autophosphorylation and a trans phosphorylation by the Src family PTK Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Furthermore , we analyze TCR proximal signaling pathways in Vav / T cells and show that despite normal activation of the Lck and ZAP 70 tyrosine kinases , the mutant cells have specific defects in TCR induced intracellular calcium fluxes , in the activation of extracellular signal regulated mitogen activated protein kinases and in the activation of the NF kappaB transcription factor . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Engagement of the T cell receptor ( TCR ) by peptide antigen bound to the major histocompatibility complex molecules initiates a biochemical cascade involving protein tyrosine kinases ( PTKs ) such as Lck , ZAP 70 and Csk , and protein tyrosine phosphatases ( PTPases ) such as CD 45 , SHP 1 and SHP 2 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The CD 5 regulated substrates included CD3zeta , ZAP 70 , Syk , and phospholipase Cgammal but not the Src family tyrosine kinase p 56 ( lck ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
ZAP 70 protein promotes tyrosine phosphorylation of T cell receptor signaling motifs ( ITAMs ) in immature CD 4 ( + ) 8 ( + ) thymocytes with limiting p 56 ( lck ) . ^^^ We report here that , in DP thymocytes , tyrosine phosphorylation of TCR signaling motifs ( ITAMs ) by lck , an early event in TCR signal transduction , is dependent upon ZAP 70 protein independent of ZAP 70 ' s kinase activity . ^^^ Furthermore , the dependence on ZAP 70 protein for ITAM phosphorylation diminishes as available lck increases . ^^^ Rather , this study indicates that ZAP 70 protein augments ITAM phosphorylation in DP thymocytes and so compensates in part for the relative deficiency of coreceptor associated lck . . ^^^
Interacting proteins: P43403 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: P43403 and P06239	Pubmed	SVM Score :0.0
Phosphorylation of Tyr 319 promoted the association of ZAP 70 with the SH 2 domains of two key signaling molecules , Lck and PLC gamma 1 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Co precipitation of Lck and ZAP 70 was only seen in T cells activated by combined A6H and anti CD 3 stimulation . ^^^ In conclusion , we now demonstrate , for the first time , that A6H ligation triggers Lck phosphorylation , and that cross talk between A6H and the TCR CD 3 complex involves Lck , ZAP 70 and the slow migrating isoform of TCR zeta . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Tyrosine 319 in the interdomain B of ZAP 70 is a binding site for the Src homology 2 domain of Lck . ^^^ T cell antigen receptor induced signaling requires both ZAP 70 and Lck protein tyrosine kinases . ^^^ One essential function of Lck in this process is to phosphorylate ZAP 70 and up regulate its catalytic activity . ^^^ We have previously shown that after T cell antigen receptor stimulation , Lck binds to ZAP 70 via its Src homology 2 ( SH 2 ) domain ( LckSH 2 ) and , more recently , that Tyr 319 of ZAP 70 is phosphorylated in vivo and plays a positive regulatory role . ^^^ Here , we investigated the possibility that Tyr 319 mediates the SH 2 dependent interaction between Lck and ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Age related impairment of p56lck and ZAP 70 activities in human T lymphocytes activated through the TcR / CD3 complex . ^^^ Of significance , the activities of p56lck and ZAP 70 in vitro were significantly decreased in T lymphocytes from elderly subjects compared to young individuals . ^^^ Our results suggest that the altered cellular immune responses observed in T lymphocytes with aging may be the result , at least in part , of an alteration in early events associated with signal transduction through the TcR / CD3 complex that translates into decreased activities of p56lck and ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Moreover , we demonstrate that this inhibitor prevented tetanus toxoid antigen specific T cell proliferation and expansion but failed to block activation of Zap 70 or p56Lck after anti CD 3 stimulation of human T cells . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
CD 44 mediated signaling involves activation of p 56 ( lck ) and leads to ZAP 70 phosphorylation . ^^^ The aim of the present study was to identify the signaling pathways that follow CD 44 triggered ZAP 70 phosphorylation and the molecular mechanisms underlying the CD 44 interaction with p 56 ( lck ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Protein tyrosine kinases p 56 ( Lck ) , SYK , and ZAP 70 and downstream adaptors LAT and SLP 76 have been implicated as essential components in T cell activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The association required intact Lck , considered to be an upstream regulator of ZAP 70 , because it could not take place in activated JCaM 1 cells , which express normal levels of ZAP 70 but are devoid of Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Coordinate activation of these pathways is dependent on Lck and ZAP 70 mediated tyrosine phosphorylation of a 36 kDa linker for activation of T cells and subsequent recruitment of phospholipase C gamma 1 , Grb 2 SOS , and SLP 76 vav . ^^^ This bypasses the need for activation of Lck and ZAP 70 , and for phosphorylation of the linker for activation of T cells to activate Ras . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Polarization of cognate T cells toward the Th 2 response occurred upon interaction of soluble DEF with TCR and CD 4 molecules followed by early activation of p 56 ( lck ) and ZAP 70 tyrosine kinases , and negative signaling of the signal transducer and activator of transcription ( STAT ) 4 pathway of Th 1 differentiation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The impaired PLC activation of cord blood derived T cells was associated with a a very low expression of the Src kinase , Lck , along with a reduced level of ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
T cell receptor ( TCR ) engagement results in the activation of Src family ( Lck and Fyn ) and ZAP 70 protein tyrosine kinases , leading to tyrosine phosphorylation of multiple cellular substrates including the complex adapter protein c Cbl . ^^^ Here , we demonstrate that kinase dead but not wild type forms of Fyn , Lck , and ZAP 70 block 70Z Cbl mediated NFAT activation . ^^^ The requirement for Fyn , Lck , and ZAP 70 is not due to tyrosine phosphorylation of 70Z Cbl , as mutation of all tyrosines in , or deletion of , the C terminal region of 70Z Cbl ( amino acids 655 to 906 ) blocks 70Z Cbl tyrosine phosphorylation but enhances 70Z Cbl mediated NFAT activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Signal transduction studies performed on FcgammaRIIc 1 expressing Jurkat cells indicated that this molecule is functional , 1 . e . capable of Ca2+ mobilization and activation of Lck , Zap 70 and Syk protein tyrosine kinases , although the CD 3 zeta chain was not found to functionally associate with FcgammaRIIc 1 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Upon stimulation of TCR by antigenic peptides , Vav associates with Zap 70 in TCR / CD3 signaling complex and becomes phosphorylated on Tyr 174 by tyrosine kinase Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Optimal activation of NF kappaB following bpV treatment necessitated downstream effectors of p 56 ( lck ) such as the syk family protein tyrosine kinase ZAP 70 and the molecular adaptor SLP 76 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Th 1 and Th 2 deviation of myelin autoreactive T cells by altered peptide ligands is associated with reciprocal regulation of Lck , Fyn , and ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The targets for the unresponsive state appear to be diminished Lck activation and absent ZAP 70 and LAT ( linker for activation of T cells ) phosphorylation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
By a two color immunofluorescence technique , expression of zeta chain , lck , and ZAP 70 was evaluated in CD3+ T cells and in three representative T cell subsets expressing TCRAV 2 , TCRBV 2 , or TCRBV 18 . ^^^ Partial loss of lck and ZAP 70 was found in CD3+ T cells from PBL of most melanoma patients , but not of healthy donors . ^^^ The extent of zeta chain , lck , and ZAP 70 loss depended on the TCRV region expressed by the T cells , and this association was maintained or increased during progression of disease . ^^^ Coculture of patients ' or donors ' T cell with melanoma cells , or with their supernatants , but not with normal fibroblasts or their supernatants , down modulated expression of zeta chain , lck , and ZAP 70 in a TCRV region dependent way . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Using Jurkat clones differing by the expression of cell surface markers or protein tyrosine kinases implicated in the CD3 / TCR signal transmission pathway , we have shown that CD 3 mAb induced inhibition of PtdSer synthesis necessitates the expression of both the CD3 / TCR and the protein tyrosine phosphatase CD 45 at the cell surface as well as the presence of p 56 ( lck ) and ZAP 70 protein tyrosine kinases . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We report inhibition of early tyrosine kinases , including ZAP 70 , p 59 ( fyn ) , CD 4 associated p 56 ( lck ) and TCR components under this condition . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The main TCR signalling pathways , such as tyrosine kinases Zap 70 and Lck , Ras / mitogen activated kinases , phospholipase Cgamma 1 and Ca2+ mobilization , were not affected in Cbl b ( / ) T cells . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
These facts were confirmed by using a panel of Jurkat clones that differs by the expression of either tyrosine kinases involved in the CD 3 induced T cell activation pathway such as p56lck , p72syk and ZAP 70 or some cell surface receptors such as the CD3 / TCR complex or the CD 45 phosphatase . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The proximal signaling events associated with A6H ligation include protein tyrosine kinase phosphorylation and association of p 56 Lck , ZAP 70 and the TCR zeta chain . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Binding of ZAP 70 to the phosphorylated immunoreceptor tyrosine based activation motifs ( ITAMs ) of the TCR zeta chain through its two src homology 2 ( SH 2 ) domains results in its activation coupled to phosphorylation on multiple tyrosine residues , mediated by Src kinases including Lck as well as by autophosphorylation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The early CD 3 induced protein tyrosine phosphorylations are conserved in both CD 4 ( + ) and CD 8 ( + ) subsets , and the levels of the T cell protein tyrosine kinases p 56 ( Lck ) , p 59 ( Fyn ) and ZAP 70 are normal . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Restoration of thymic development in an Lck ( / ) thymoma overexpressing ZAP 70 . ^^^ The major players in this process are Lck and ZAP 70 , which regulate critical differentiation steps of thymopoiesis . ^^^ Notwithstanding the critical role of Lck and ZAP 70 in thymocyte development as compared to the related kinases Fyn and Syk , a partial functional redundancy between members of the same family of protein tyrosine kinases has emerged from studies on genetically manipulated mouse models . ^^^ Furthermore , a close functional interplay between Lck and ZAP 70 in intracellular signaling has been shown to occur in thymocytes . ^^^ Determination of the expression levels of Fyn , ZAP 70 and Syk in thymocytes form the Lck ( / ) thymoma revealed high levels of ZAP 70 overexpression and recovery of a specific subset of phosphoproteins as compared to Lck ( / ) thymocytes . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
ITIMs with the restricted consensus sequence occur on IL 4Ralpha , IL 3Rbeta type 2 , gp 130 cytokineR , OB R ( leptinR ) , LIF Rbeta TNF RI , G CSF R , PDGF R , Blk , Ctk / Ntk , Lsk , Zap 70 , PKB / RACalpha , PKC alpha , PKC beta , PKC gamma , PKC delta , PKC zeta , PKC epsilon , PKC eta , PKC phi , PKC mu , calmodulin dependent kinase IIdelta , SLP 76 associated protein , FYN binding protein , Shc binding protein , RasGRF 2 , CDC 25 homologue , Jak 2 , Jak 3 , PLCbeta 1 , and PLCbeta 3 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The defect in ERK activation was associated with impaired recruitment of the activated tyrosine kinases Lck and ZAP 70 , phosphorylated forms of the TCR component CD3zeta and the adaptor protein LAT to detergent insoluble glycolipid enriched microdomains ( DIGs ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In this study , we investigated the role played by the protein tyrosine kinases Fyn , Lck , and ZAP 70 in antagonist induced signaling pathway . ^^^ Antagonist stimulation increased tyrosine phosphorylation and kinase activity of Fyn severalfold , whereas little or no increase in Lck and ZAP 70 activity was observed . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Co expression of protein tyrosine kinases , Lck and Zap 70 , with HPK 1 led to HPK 1 activation and tyrosine phosphorylation in transfected mammalian cells . ^^^ T cell specific signaling molecules Lck , Zap 70 , and LAT play roles in the regulation of HPK 1 during TCR signaling . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Engagement of the T cell antigen receptor ( TCR ) induces the transphosphorylation of the zeta chain associated protein of 70 , 000 Mr ( ZAP 70 ) protein tyrosine kinase ( PTK ) by the CD4 / 8 coreceptor associated Lck PTK . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Antagonists of the Src homology 2 ( SH 2 ) domains of Grb 2 , Src , Lck and ZAP 70 . ^^^ Among the SH 2 domains pursued as drug discovery targets in the last few years are those of Grb 2 , Src , Lck and ZAP 70 . ^^^
Interacting proteins: P43403 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 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Biochemical characteristics of the receptors , analyzed using calcium flux , receptor , and ZAP 70 phosphorylation , and lck association may be predicted from the known functions of receptor constituents . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Our results therefore indicate a mechanism whereby CD 26 engagement promotes aggregation of lipid rafts and facilitates colocalization of CD 45 to T cell receptor signaling molecules p 56 ( Lck ) , ZAP 70 , and TCRzeta , thereby enhancing protein tyrosine phosphorylation of various signaling molecules and subsequent interleukin 2 production . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In this study , we investigated the participation of Lck and ZAP 70 protein tyrosine kinases ( PTKs ) , as well as PLC gamma 1 and Shc proteins in PBMC activation by Schistosoma mansoni antigens . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Upon CD 3 CD4 ligation , TCR zeta phosphorylation , ZAP 70 recruitment to the p21 / p23 TCR zeta phosphoisomers , ZAP 70 phosphorylation , as well as p 56 ( lck ) , c Cbl and Slp 76 phosphorylation , were all markedly increased in CD45R0 ( + ) compared with CD45RBC ( + ) cells . ^^^ Upon CD 3 CD4 co ligation , the active p 56 ( lck ) increases the intensity of T cell antigen receptor signal transduction coupling by promoting TCR zeta chain phosphorylation and ZAP 70 recruitment . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Superantigen induced T cell : B cell conjugation is mediated by LFA 1 and requires signaling through Lck , but not ZAP 70 . ^^^ However , ZAP 70 deficient cells conjugate normally , indicating that Lck is required for LFA 1 dependent adhesion via other downstream pathways . ^^^ Although the way in which Lck signals to enhance LFA 1 dependent adhesion is not clear , we find that cells lacking functional Lck fail to recruit F actin and LFA 1 to the T cell : APC contact site , whereas ZAP 70 deficient cells show a milder phenotype characterized by disorganized actin and LFA 1 at the contact site . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Studies on three different Jurkat cell mutants deficient for src p 56 ( lck ) , ZAP 70 kinase , or TCR / CD3 gamma chain showed that the cells undergo apoptosis after Fas ligation . ^^^ Simultaneous cross linking of MHC 1 and Fas ligation inhibited apoptosis in the ZAP 70 kinase and the TCR / CD3 gamma chain mutants , but did not protect the src p 56 ( lck ) deficient cells . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In order to investigate potential effects of mycobacteria on T cell receptor signalling , we examined the protein expression of T cell signal transduction molecules ( CD3zeta , ZAP 70 , p59fyn , p56lck ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In contrast to the ZAP 70 / diphosphorylated CD 8 epsilon ITAM interaction , the Lck / monophosphorylated CD 8 epsilon ITAM interaction was sensitive to octylglucoside , an agent that disrupts Lck interaction with membrane rafts . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Finally , analysis of a ZAP 70 deficient T cell line revealed that Cbl inhibited Lck dependent mitogen activated protein kinase activation , and an intact Cbl RING finger domain was required for this functional effect . ^^^ Our results demonstrate a direct , ubiquitination dependent , negative regulatory role of Cbl for Lck in T cells , independent of Cbl mediated regulation of ZAP 70 . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
However , the association of p 56 ( lck ) with ZAP 70 was inhibited following CTLA 4 ligation , correlating with reduced actions of p 56 ( lck ) in the ZAP 70 immunocomplex . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Despite the dependence on functional Lck and on phosphorylated ITAM for Pyk 2 translocation , the ITAM binding tyrosine kinase zeta associated protein 70 ( ZAP 70 ) was not essential . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
These kinases require prior activation of Lck , Zap 70 and PI 3 kinase for efficient activation . ^^^ They share major substrates with both Lck and Zap 70 , however the pathways they regulate are unclear . ^^^ Recent evidence suggests that these kinases may not activate unique pathways , but instead serve as amplifiers for the upstream kinases Lck and Zap 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Downstream of TCR , we find that p56Lck ( Lck ) plays a critical role in integrin dependent adhesion independent of its ability to activate zeta associated protein of 70 kDa ( ZAP 70 ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Here , we studied intracellular signaling in SMACs by three dimensional immunofluorescence microscopic localization of CD 3 , CD 45 , talin , phosphotyrosine , Lck and phosphorylated ZAP 70 in T cell APC conjugates . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Noteworthy are peptidomimetic and nonpeptide inhibitors of Src , Lck , Grb 2 , PI 3K , and Zap 70 from pioneering efforts that led to the first examples of cellularly and in vivo active SH 2 inhibitors . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The active participation of p 56 ( lck ) , ZAP 70 , p 36 ( LAT ) , and calcium in the bpV dependent signaling cascade leading to COX 2 transcriptional activation was demonstrated using deficient cell lines and specific inhibitors . ^^^ Although several PTPs are most likely targeted by bpV , our data suggest that the bpV mediated signaling cascade is initiated by inhibition of SHP 1 , which leads to phosphorylation of p 56 ( lck ) and ZAP 70 and , ultimately , to NFAT and activator protein 1 nuclear translocation . ^^^
Interacting proteins: P43403 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 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
CD 45 has also been shown to regulate CXCR 4 mediated activation and phosphorylation of T cell receptor downstream effectors Lck , ZAP 70 , and SLP 76 . ^^^
Interacting proteins: P43403 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 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In all nine T ALL samples studied , the leukaemic cells showed a marked reduction in the expression of the zeta chain , while a variety of tyrosine kinases ( p56lck , ZAP 70 and SYK ) were normally present . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Anti CD 4 was found to perturb proximal signalling events upon TCR / CD3 ligation , resulting in reduced tyrosine phosphorylation of Zap 70 and LAT ( linker for activation of T cells ) and reduced association of tyrosine phosphorylated LAT with lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We analyzed jacalin induced intracellular signaling events in CD 4 ( + ) T cells and have shown that cell activation resulted in tyrosine phosphorylation of intracellular substrates p 56 ( lck ) , p 59 ( fyn ) , ZAP 70 , p 95 ( vav ) , phospholipase C gamma 1 , and ras activation , as assessed by conversion of ras guanosine 5 ' diphosphate to ras guanosine 5 ' triphosphate . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
These unpublished data indicate that sHLA I / CD8 ligation elicits the phosphorylation of p56lck protein thyrosin kinase ( PTK ) associated with CD 8 cytoplasmic domain in the absence of any other TCR derived signal , the activation of syk like ZAP 70 PTK and protein kinase C , and extracellular calcium influx . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We have already determined that p 56 ( lck ) , ZAP 70 , SLP 76 , capacitative entry of calcium , and calcium regulated effectors are important in bpV induced NF kappaB activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Taken together , these results suggest that rosmarinic acid has the potential to specifically inhibit Lck SH 2 domain binding to its cognate ligand , including ZAP 70 , Cbl , HS 1 , and PLCgamma 1 , and Lck dependent Ca 2+ signaling pathway of its downstream effector and finally to modulate IL 2 gene expression after T cell activation . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We identified known signaling molecules such as Lck , ZAP 70 , Syk , PLC gamma 1 and SHP 1 ( PTP1C ) as truncation mutants with dominant negative or constitutively active functions . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We also showed that CD 26 cross linking induced less phosphorylation of T cell receptor signaling molecules , lymphoid T cell protein tyrosine kinase ( Lck ) , zeta associated protein 70 ( ZAP 70 ) , T cell receptor zeta ( TCRzeta ) , and linker for activator of T cells ( LAT ) in CBTCs than in PBTCs . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
While crosslinking of Fas affected the association of p59fyn and p56lck tyrosine kinases with the TCR zeta chain to a limited degree , it dramatically inhibited the association of the protein tyrosine kinase ZAP 70 with the zeta chain . ^^^
Interacting proteins: P43403 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: P43403 and P06239	Pubmed	SVM Score :0.0
Interaction of human MUC 1 and beta catenin is regulated by Lck and ZAP 70 in activated Jurkat T cells . ^^^ In the present work , MUC 1 was studied as a potential downstream effector of the Lck and ZAP 70 tyrosine kinases that are essential for T cell activation . ^^^ In contrast to Lck , ZAP 70 phosphorylates MUC 1 CD predominantly on Y 20 . ^^^ However , like Lck , ZAP 70 mediated phosphorylation of MUC 1 Y 20 stimulates binding of MUC 1 and beta catenin . ^^^ These findings indicate that MUC 1 functions as a substrate for Lck and ZAP 70 in activated Jurkat T cells and that MUC 1 integrates T cell receptor signaling with the beta catenin pathway . . ^^^
Interacting proteins: P43403 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 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Here we demonstrate that , due to the sequestration of Lck by HVS Tip , T cell receptor ( TCR ) stimulation fails to activate ZAP 70 tyrosine kinase and to initiate downstream signaling events . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
These results implicate Dok 1 , Nck , Crk L , and Src kinases especially Lck , Pyk 2 , Zap 70 , Vav , and Ras GAP in intracellular signaling by SDF 1alpha / CXCL12 , and they suggest that Dok 1 plays an important role in SDF 1alpha / CXCL12 induced chemotaxis in T cells . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
The interaction of T cells with target cells that overexpress costimulatory molecules upon infection with rF TRICOM leads to enhanced signaling through Lck , ZAP 70 , and STAT 1 in CD8+ T cells and heightened lytic activity of CD8+ cells through the formation of a greater number of immunological synapses . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Crosslinking of purified wild type nave CD 4 cells with anti CD 3 activated Lck and initiated the signaling cascade downstream of Lck , including phosphorylation of ZAP 70 , LAT , and PLC gamma 1 ; calcium flux ; and dephosphorylation and nuclear translocation of the nuclear factor of activated T cells ( NFAT ) p . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
To dissect the early signalling events leading to TNF alpha gene expression , we established that CD 45 crosslinking resulted in tyrosine phosphorylation of p56lck , ZAP 70 , CD 3 zeta , LAT and Vav . ^^^ This was accompanied by down regulation of membrane associated protein tyrosine phosphatase activity in the absence of demonstration of enhanced p56lck , p72syk and ZAP 70 kinase activity , which remained constitutive . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Sequence comparisons of all 90 tyrosine kinase genes in the human genome for homology in the adenosine triphosphate ( ATP ) binding pocket identified LCK , which is required for ZAP 70 activation , as a likely target for imatinib . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Confocal microscopy and fluorescence resonance energy transfer analyses demonstrate that TIL are triggered by conjugate formation in that the TCR , p56lck , CD3zeta , LFA 1 , lipid rafts , ZAP 70 , and linker for activation of T cells localize at the TIL : tumor cell contact site , and CD 43 and CD 45 are excluded . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Importantly , the membrane translocation of Vav 3 was abrogated in Lck , ZAP 70 , LAT , and SLP 76 deficient T cells , where Vav 3 binding to SLP 76 was disrupted . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Thus , phosphorylation of Tyr 323 dependent on the tyrosine kinase Lck and mediated by Zap 70 serves as an important mechanism for TCR activation of p 38 in T cells . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In these patients , ZAP 70 fails to be recruited to the TCR as the result of impaired CD3zeta phosphorylation , which is , however , not dependent on defective Lck expression or activity . ^^^
Interacting proteins: P43403 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 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Consistent with this possibility , ZAP 70 recruitment was also detected with anti CD 3 stimulated , Lck deficient human Jurkat T cells . ^^^ We conclude that TCR / CD3 induced CD3zeta phosphorylation and ZAP 70 recruitment do not absolutely require Lck or other PP 2 inhibitable SFK activity , but that SFK activity is absolutely required for CD3epsilon and ZAP 70 phosphorylation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Here , we show that T cell receptor triggering results in rapid degradation of the src family protein kinase lck through a mechanism that is proteasome and lysosome independent , sensitive to cysteine protease inhibitors , and distinct from the pathways involved in degradation of ZAP 70 kinase or zeta chain of the CD 3 complex . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We also provide evidence that SLAP functions in a pathway that requires the phosphorylated TCRzeta chain and the Src family kinase Lck , but not ZAP 70 ( zeta associated protein of 70 kD ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In addition , an Lck deficient Jurkat cell line that can not efficiently activate ZAP 70 was also found defective in RXRE mediated transcription . ^^^ Finally , RNA interference induced loss of ZAP 70 or Lck protein in Jurkat cells resulted in significant decrease in the RXRE dependent activation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
CAML deficient cells displayed enhanced p56lck and ZAP 70 phosphorylation and increased IL 2 production and cell death after TCR stimulation , suggesting that CAML may act as a negative regulator of p56lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
CA 125 did not reduce proliferation or induce apoptosis of NK cells and alter the expression of p56lck , phospholipase Cgamma 1 , ZAP 70 , or CD3zeta . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
At 0 30 s after contact , TCR microclusters are colocalized with activated forms of Lck , ZAP 70 , and the linker for activation of T cells . ^^^ By 5 min , TCR in the central supramolecular activation cluster have reduced activated kinases , whereas faint peripheral TCR microclusters efficiently generated activated Lck and ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Distinct spatial and temporal distribution of ZAP 70 and Lck following stimulation of interferon and T cell receptors . ^^^ T cell receptor ( TCR ) stimulation results in the recruitment and activation of the proteins ZAP 70 and Lck . ^^^ To address this question , the proteins ZAP 70 and Lck were investigated following stimulation of the interferon alpha receptor and the TCR in T cells by two different extracellular stimulants : interferon alpha and the anti CD 3 antibody , OKT 3 , respectively . ^^^ Translocation of both ZAP 70 and Lck to the nucleus following interferon receptor stimulation is demonstrated for the first time . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Biochemically , these traits were associated with higher basal phosphorylation of the TCR signaling proteins ZAP 70 , Lck , and LAT . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
We show that Crry increases early TCR dependent activation signals , including p56lck , zeta associated protein 70 ( ZAP 70 ) , Vav 1 , Akt , and extracellular signal regulated kinase ( ERK ) phosphorylation but also costimulation dependent mitogen activated protein kinases ( MAPK ) , such as the stress activated c Jun N terminal kinase ( JNK ) . ^^^ The Crry cytoplasmic domain was required for JNK activation and interleukin 4 secretion but not for the presence of Crry in rafts or activation of p56lck , ZAP 70 , Akt , Vav 1 , or ERK . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Molecular analysis of the biochemical pathways responsible for FasL up regulation showed that sHLA I / CD8 interaction firstly induced the recruitment of src like p 56 ( lck ) and syk like Zap 70 protein tyrosine kinases ( PTK ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
T cell activation induced CrkII binding to the Zap 70 protein tyrosine kinase is mediated by Lck dependent phosphorylation of Zap 70 tyrosine 315 . ^^^ Phosphorylation of Tyr 315 and Zap 70 association with CrkII were both dependent upon the Lck protein tyrosine kinase . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
In the Jurkat T cell leukemia line , the multiplex assay enabled targeted investigation of phosphorylation kinetics of signal transduction from receptor proximal events ( tyrosine phosphoproteins CD 3 , Lck , Zap 70 , and linker for T cell activation ) to cytosolic events ( serine / threonine phosphoproteins Erk and Akt ) to transcription factors ( serine / threonine phosphorylated Rsk , cyclic AMP response element binding protein , and STAT 3 ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Mutant T cell lines contained a more active pool of p56lck tyrosine kinase and responded with increased phosphorylation of Zap 70 and TCR zeta and an enhanced Ca2+ flux to TCR / CD3 stimulation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
DX induced ZAP 70 phosphorylation did not occur in the absence of active p 56 lck as examined in the p 56 lck kinase deficient Jurkat cell line JCaM1 . 6 . ^^^ Lck and ZAP 70 represent an important molecular link between the TcR and GC signalling pathways . . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Both CD 69 up regulation and ZAP 70 phosphorylation were suppressed in Lck ( lo ) cells when compared with those in Lck ( hi ) cells upon TCR stimulation . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
This data suggests an interference of PGE ( 2 ) at an early step of T cell receptor signaling : indeed , PGE ( 2 ) stimulation of T cells leads to inactivation of lck and reduced phosphorylation of ZAP 70 . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
These included three novel PTPN 22 substrates ( Vav , CD3epsilon , and valosin containing protein ) and two known substrates of PEP , the mouse homolog of PTPN 22 ( Lck and Zap 70 ) . ^^^ In vitro experiments with purified recombinant proteins demonstrated that PTPN 22 D195A / C227S interacted directly with activated Lck , Zap 70 , and TCRzeta , confirming the initial substrate trap results . ^^^ Native PTPN 22 dephosphorylated Lck and Zap 70 at their activating tyrosine residues Tyr 394 and Tyr 493 , respectively , but not at the regulatory tyrosines Tyr 505 ( Lck ) or Tyr 319 ( Zap 70 ) . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Protein analyses indicate that in addition to FcRgamma , DN Treg cell clones also express higher levels of TCRbeta , while mutant clones expressed higher levels of Zap 70 and Lck . ^^^
Interacting proteins: P43403 and P06239	Pubmed	SVM Score :0.0
Here we demonstrate that defects in cluster assembly and persistence are associated with defects in T cell activation in the absence of Lck , ZAP 70 , or LAT . ^^^