Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.81836472
Association of CD 45 with Lck and components of the Ras signalling pathway in pervanadate treated mouse T cell lines . 0.81836472^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
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Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.52064047
Here , using co capping experiments and double indirect immunofluorescence microscopy in functional human T lymphocytes , a specific co distribution of a significant fraction of p56lck with CD 45 , but not with several other cell surface proteins , has been revealed . 0.52064047^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :1.0892144
We show now that CD 45 associates with lck independently of both CD 4 and CD 8 . 1.0892144^^^ The association between CD 45 and lck does not require CD 4 or CD 8 and is independent of T cell receptor stimulation . 0.74089362^^^ We have shown that CD 45 physically associates with lck , one src kinase . 0.69317994^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.72679369
In this study , recombinant purified p56lck was found to specifically associate with recombinant CD 45 cytoplasmic domain protein , but not to the cytoplasmic domain of another related tyrosine phosphatase , receptor protein tyrosine phosphatase alpha . 0.72679369^^^ Demonstration of a direct interaction between p56lck and the cytoplasmic domain of CD 45 in vitro . p56lck is a potential in vivo substrate for the tyrosine specific phosphatase , CD 45 . 0.55227131^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.55555794
In addition to providing insights into the nature and regulation of the interactions between CD 45 and p 56 ( lck ) in T cells , these results indicated that CD 45 clearly has the capacity to both positively and negatively regulate p 56 ( lck ) mediated functions in vivo . . 0.55555794^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.91740301
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 . 0.91740301^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.54807051
Interestingly , the interaction between CD 45 and Lck was significantly reduced in CD 45 AP null T cells , indicating that CD 45 AP directly or indirectly mediates the interaction of CD 45 with Lck . 0.54807051^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.72207593
Tyrosine kinase p56lck plays a pivotal role in beta selection from CD 4 8 ( DN ) to CD4+8+ ( DP ) developing pathway , but it is unclear how CD 45 transmembrane tyrosinephosphatase is involved in this process although CD 45 activates p56lck by dephosphorylating its tyrosine 505 . 0.72207593^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.83014163
These results demonstrate that CD 45 AP associates directly and selectively with Lck and ZAP 70 in response to T cell receptor mediated stimulation . 0.83014163^^^ 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 . . 0.51637478^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.52517113
Importantly , and in disagreement with the model that CD 45 only activates Lck in vivo , the kinase activity of Lck from cells lacking CD 45 was substantially increased . 0.52517113^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.72093037
Interestingly , the ability of CD 45 AP to interact with Lck in the absence of other lymphoid specific molecules was proportional to the degree of catalytic activation of p 56 ( lck ) . 0.72093037^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Signaling through ICAM 3 stimulates a number of T cell functions and involves phosphorylation of Fyn , Lck , CD 45 , and other proteins . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The phosphatase activity of CD 45 has been implicated to regulate p56lck tyrosine kinase activity by removing an inhibitory phosphate . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
In human T cells CD 45 is reported to associate with both cell surface and intracellular molecules including CD 2 , CD4 / CD8 , CD 5 , p56lck and p59fyn . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Signaling through the TcR CD 4 D8 lck CD 45 complex is thought to be insufficient to activate T lymphocytes . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Upon activation through the CD 2 or the CD 45 receptors the kinase activity of p56lck is temporarily increased . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The role of p56lck and p59fyn tyrosine kinases and CD 45 protein tyrosine phosphatase in T cell development and clonal selection . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Differences in phosphorylation were not due to purification artifact lymphocyte src family kinase , p56lck or the protein tyrosine phosphatase CD 45 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The inability to activate p 56 ( lck ) in CD 45 deficient cells results in a higher threshold of signaling through the T cell receptor . ^^^
Interacting proteins: P08575 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: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 directly inactivated p 59 ( hck ) but not p 56 ( lck ) in transient transfection assays . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Furthermore , we found differential contributions of CD 45 and p56lck to development and induction of cytolytic activities of 1 IEL . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The CD 45 protein tyrosine phosphatase ( PTPase ) has been shown to regulate the activity of Lck and Fyn protein tyrosine kinases in T cells . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Furthermore , thymocyte CD 45 associated p 56 ( lck ) kinase activity was similar between CD45AP deficient and normal cells . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Data show that cross linking of CD 45 markedly inhibits CD40L induced activity of the Src family kinases Lck and Lyn . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
We found that TCR cross linking alone could not stimulate Lck autophosphorylation and CD 45 was not required for this process . ^^^
Interacting proteins: P08575 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: P08575 and P06239	Pubmed	SVM Score :0.0
Thus , gp 180 expression by IBD IEC appears to be altered , and correlates with a functional alteration of lck activation . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
This process appears to relate in part to a 180 kDa IEC surface glycoprotein , gp 180 , which binds to CD 8 and activates CD 8 associated p 56 ( lck ) . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
It has been previously shown that monoclonal antibodies against gp 180 inhibited the activation of CD 8 associated p 56 ( lck ) in T cells . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The CD 45 transmembrane protein tyrosine phosphatase ( PTPase , EC 3 . 1 . 3 . 48 ) plays an essential role in T cell activation by activating the Lck and / or Fyn protein tyrosine kinases . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Dephosphorylation and activation of the T cell tyrosine kinase pp56lck by the leukocyte common antigen ( CD 45 ) . pp56lck , encoded by the lck proto oncogene , is a non receptor tyrosine protein kinase ( TPK ) found in all T lymphocytes . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
In human T lymphocytes a functional complex is formed between the protein tyrosine phosphatase CD 45 , the protein tyrosine kinase p56lck and a phosphoprotein , pp 32 , a possible common substrate . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 2 can mediate TcR CD 3 independent and CD 45 dependent activation of p56lck . ^^^ By isolating CD 45 mutants from Jurkat cells , we observed that surface expression of the tyrosine phosphatase CD 45 is required in order to increase p56lck activity following CD 2 stimulation , while CD 4 induced activation of the kinase remained unchanged . ^^^ These data provide evidence for a specific functional linkage between CD 2 and p56lck , in which CD 45 may play an essential role . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The machinery which couples the TcR / CD3 complex , CD 4 , and CD 45 to PI PLC appears to involve regulation of tyrosine phosphorylation , as the TcR / CD3 and CD 4 receptors are associated with the tyrosine kinases p59fyn and p56lck , respectively , and CD 45 has intrinsic tyrosine phosphatase activity . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The tyrosine kinase activity of p59fyn was found to be 65 % less in CD 45 cells than in CD45+ cells , whereas p56lck kinase activity was comparable in both sub clones . ^^^ Co aggregation of CD 4 or CD 8 p56lck kinase with the TCR in CD 45 cells restored TCR induced protein tyrosine phosphorylation , phospholipase C gamma 1 regulation and calcium signals . ^^^ These results indicate that CD 45 regulated p59fyn plays a critical role in coupling the TCR to specific intracellular signalling pathways and that CD 4 or CD 8 p56lck can only restore signal transduction coupling in CD 45 cells when brought into close association with the TCR . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Altered expression of protein kinase C , lck , and CD 45 in a 12 O tetradecanoylphorbol 13 acetate dependent leukemic T cell variant that expresses a high level of interleukin 2 receptor . ^^^ In addition , P 13 5 / A8 cells display very little , if any , surface expression of CD 45 , a receptor linked tyrosine protein phosphatase , and lck , a lymphocyte specific tyrosine kinase . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Interaction of CD 4 : lck with the T cell receptor / CD3 complex induces early signaling events in the absence of CD 45 tyrosine phosphatase . ^^^ Anti CD 4 induced tyrosine phosphorylation and activation of CD 4 associated lck was also enhanced in CD 45 cells , suggesting that increased lck activation compensates for the defect in CD3 / TcR signaling , such that interaction of the CD 3 signaling pathway with the CD 4 associated pathway activates PLC even in the absence of CD 45 . ^^^ In normal T cells , CD 3 mediated PLC activation is significantly augmented by co ligation of CD 3 with the CD 4 co receptor ; however , unlike CD 3 associated tyrosine kinases , antibody induced activation of the CD 4 associated tyrosine kinase p56lck does not require CD 45 expression . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The invariant part of the T cell receptor is associated with the tyrosine kinase p59fyn , the coreceptors are associated with the tyrosine kinase p56lck , and the cytoplasmic domain of CD 45 has tyrosine specific phosphatase activity . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Evidence is increasing that the Src related protein tyrosine kinases P56lck and p59fyn , as well as the protein tyrosine phosphatase CD 45 , are involved in this process . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Moreover , it was suggested , in the experiments using CD 45 cross linking or a protein tyrosine kinase inhibitor , genistein , that p56lck affects syncytium formation through its protein tyrosine kinase activity . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
A functional complex is formed in human T lymphocytes between the protein tyrosine phosphatase CD 45 , the protein tyrosine kinase p56lck and pp 32 , a possible common substrate . ^^^ Reprecipitation of the in vitro phosphorylated proteins and Western blot analysis of whole CD 45 immunoprecipitates employing antisera specifically directed at different protein tyrosine kinases demonstrated that the p56lck protein tyrosine kinase was responsible for in vitro phosphorylation of pp 32 . ^^^ Since in vitro kinase assays of p56lck immunoprecipitates also resulted in phosphorylation of pp 32 , the present data strongly suggest that a functional complex is formed between CD 45 , p56lck and pp 32 . ^^^ Such a notion is supported by the findings that phosphorylation of pp 32 by p56lck correlated with expression of the CD 45 molecules and that in vitro phosphorylated pp 32 was completely dephosphorylated by purified CD45 . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The protein tyrosine kinase activity associated with CD 4 and CD 8 ( p56lck ) and the phosphatase activity of CD 45 have been implicated elsewhere in jointly regulating peripheral T cell signal transduction and subsequent cellular responses . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Because the presence of CD 45 is crucial for the function of the lymphocyte specific tyrosine kinase p56lck , which is associated with lymphocyte growth and transformation , this may be the molecular basis for the non aggressive nature of this clonal T cell proliferation . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
This association may allow CD 45 to engage and dephosphorylate lck or another CD 4 or CD 8 associated substrate in order to reset the receptor complex to receive a new set of stimuli . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
This conclusion is consistent with our observation that in activated human T cells , class 2 signals are up regulated by CD 4 , which is associated with p56lck , and down regulated by CD 45 , which is a tyrosine phosphatase . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Coclustering CD 45 with CD 4 or CD 8 alters the phosphorylation and kinase activity of p56lck . ^^^ Treatment with anti CD 4 and anti Ig also induced the phosphorylation of p56lck in a CD 45 mutant cell line , indicating that the increase in phosphotyrosine content of p56lck is not the result of being sequestered from CD 45 protein tyrosine phosphatase ( PTPase ) . ^^^ Antibody mediated coclustering of CD 45 with CD 4 inhibited the anti CD 4 induced phosphorylation of p56lck on tyrosine and the concomitant increase in in vitro kinase activity . ^^^ These observations provide strong evidence that p56lck is a substrate for CD 45 in vivo and provide an assay to study the regulation and specificity of CD 45 PTPase activity . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Autophosphorylated preparations of epidermal growth factor receptor , insulin receptor , and p56lck protein tyrosine kinases were also substrates for CD 45 in vitro . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Studies with three independent sets of well characterized parental CD45+ , mutant CD 45 , and revertant CD45+ lymphoma cell lines indicate that loss of CD 45 increases the phosphorylation of the src related leukocyte specific tyrosine protein kinase p56lck on tyrosine 505 , a putative negative regulatory site . ^^^ This suggests that CD 45 may play a role in leukocyte growth regulation by altering the kinase activity of p56lck . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
By contrast , the CD 45 antigens possess protein tyrosine phosphatase activity within their intracellular domains and are postulated to function by virtue of a regulatory interaction with CD4 / CD8 : p56lck and its potential substrates . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The results clearly demonstrated that among PTKs examined ( Lyn , Lck , and Syk ) , only Lyn kinase is dysregulated in the absence of CD 45 such that without B cell antigen receptor ligation , Lyn is hyperphosphorylated and activated in CD 45 negative clones . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 activates the Src family protein tyrosine kinases , p56lck and p59fyn , by dephosphorylating a negative regulatory tyrosine in the carboxyl terminus . ^^^ Immunoprecipitation of CD 45 precipitates p56lck and CD45AP . ^^^ Although the function of CD45AP is unknown , it has been proposed to be an adapter between p56lck and CD 45 . ^^^ These data support a model in which CD45AP links CD 45 with other proteins but not necessarily p56lck . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of CD 45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase . ^^^ Tyrosine phosphorylated CD 45 bound p56lck through the SH 2 domain of the kinase . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Immunokinase assays of Lck and Fyn precipitated from untreated or anti CD 45 treated wild type transfectants demonstrated that CD 45 cross linking dephosphorylated Lck and reduced its capacity to phosphorylate enolase . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
We have compared two mutant Jurkat cells , one largely deficient in expression of CD 45 ( J45 . 01 ) and a second one deficient in expression of p56lck ( JCaM1 . 6 ) with wild type Jurkat cells for their ability to undergo APO 1 induced apoptosis . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Immobilized antibodies to CD 45 induce rapid morphologic changes and increased tyrosine phosphorylation of p56lck associated proteins in T cells . ^^^ The phosphoproteins induced when cells are added to immobilized anti CD 45 are co immunoprecipitated with p56lck , suggesting that this tyrosine kinase might play a role in the phosphorylation of these proteins . ^^^ Consistent with this , there is no increase in the phosphorylation of these proteins in p56lck deficient CTLL 2 cells in response to immobilized anti CD 45 mAb . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Cross linking of CD 45 on NK cells stimulates p56lck mediated tyrosine phosphorylation and IFN gamma production . ^^^ Biochemical analyses and immunofluorescence studies suggest that the tyrosine kinase associated with CD 45 is p56lck and that cross linking of CD 45 results in the activation of p56lck . ^^^ Thus , CD 45 may regulate p56lck kinase , which initiates the cascade of intracellular tyrosine phosphorylation events that lead to IFN gamma transcription and secretion in NK 3 . 3 cells . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The intracellular localization of some of these molecules is supported by the fact that the 56 kDa molecule seen in CD 45 mAb immunoprecipitates from lysates of Jurkat cells biotinylated in the presence of lysolecithin could be identified as the src like tyrosine kinase p56lck by immunoblotting with p56lck Abs . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Since the myristylation defective mutant also failed to stably associate with cellular membranes , this effect was most probably the consequence of removal of p56lck from the vicinity of membrane phosphatases like CD 45 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The poor expression of the p56lck gene by the prothymic blasts compared with the thymic blasts may be related to the expression pattern of the CD 45 RA / RO molecules , which exhibits phosphatase activity . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Impaired development of 5 gamma 3 dendritic epidermal T cells in p56lck protein tyrosine kinase deficient and CD 45 protein tyrosine phosphatase deficient mice . ^^^ To determine whether p56lck protein tyrosine kinase and CD 45 protein tyrosine phosphatase are involved in the signal transduction during intrathymic differentiation of gamma / delta T cells , we have examined the development of T cells expressing 5 gamma 3 T cell receptor ( TCR ) in mice deficient for either protein . ^^^ These results imply that both p56lck and CD 45 are involved in the signal transduction during maturation of 5 gamma 3 T cells in the fetal thymus . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
T cell activation Structure of the T cell antigen receptor Modular organisation of the T cell antigen receptor T cell antigen receptor coupled signaling pathways : Activation of protein tyrosine kinase by the T cell antigen receptor ; Signal transduction in lymphoid cells involves several protein tyrosine kinases in parallel ; Regulation of T cell antigen receptor signaling by the phosphoprotein phosphatase CD 45 Consequences of T cell antigen receptor induced tyrosine phosphorylation : Activation of phosphoinositol lipid turnover pathways Activation of phospholipase C gamma 1 : p59fyn or p56lck ? ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
By examining Lck autophosphorylation , we find that Fc epsilon RI aggregation induces an increase in Lck enzymatic activity only in wild type Jurkat and the CD 45 deficient Jurkat reconstituted with chimeric CD 45 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Activation and internalization of p56lck upon CD 45 triggering of Jurkat cells . ^^^ Relationships between CD 45 and p56lck have been suggested by co immunoprecipitation of both proteins and by dephosphorylation of the p56lck regulatory site , Tyr 505 , by CD 45 in vitro . ^^^ We investigated whether the kinase activity of p56lck is modulated in T cells triggered via CD 45 . ^^^ We showed that incubation of Jurkat cells with a combination of two anti CD 45 monoclonal antibodies ( mAb ) ( MC5 / 2 + D3 / 9 ) induced an increase in p56lck kinase activity , while a single mAb did not . ^^^ Similarly , activation and internalization of p56lck were observed using a combination of anti CD 45 ( MC5 / 2 ) and anti CD 2 ( T 11 ( 2 ) ) mAb , suggesting that a functional complex consisting of CD 45 , CD 2 and p56lck was formed upon cell triggering . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Two members of the Src family of protein tyrosine kinases ( PTKs ) , the p56lck and p59fyn proteins , have been implicated as physiological substrates of CD 45 , providing an important clue to how the action of this leukocyte specific PTP might influence signaling by the T cell antigen receptor . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 73 transfectants of Jurkat mutants defective in the TCR , in p56lck , or in the tyrosine phosphatase CD 45 did not secrete IL 2 in response to CD 73 mAb + PMA , suggesting a role for the CD3 / TCR signaling complex in CD 73 mediated signal transduction . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Here we show that antibody engagement of CD 45 external domains enhances Lck tyrosine kinase activity in CD4+CD8+ thymocytes , inhibits TCR expression , and inhibits differentiation of immature CD4+CD8+ thymocytes into mature T cells . ^^^ TCR expression by CD4+CD8+ thymocytes is quantitatively regulated by CD 4 mediated activation of p56lck protein tyrosine kinase whose activity can in turn be regulated by the membrane bound protein tyrosine phosphatase CD 45 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
We also demonstrate that the phosphorylation of the C terminal tyrosine of Lck , a site of negative regulation , is reduced only when CD 45 mutants with demonstrable in vitro phosphatase activity are introduced into the CD 45 deficient cells . ^^^ These results demonstrate that the phosphatase activity of CD 45 is critical for TCR signaling , and for regulating the levels of C terminal phosphorylated Lck molecules . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The CD 45 tyrosine phosphatase regulates specific pools of antigen receptor associated p59fyn and CD 4 associated p56lck tyrosine in human T cells . ^^^ Unexpectedly , whole cell p56lck and p59fyn tyrosine kinase activities were not reduced in CD 45 compared to CD45+ cells . ^^^ Using this technique it was shown that cell surface CD 4 p56lck kinase activity was 78 % lower in CD 45 than in CD45+ cells . ^^^ Our results demonstrate that CD 45 selectively regulates the pools of p59fyn and p56lck kinases which are associated with the TCR and CD 4 at the cell surface . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Lck from CD 45 cells was hyperphosphorylated on the cyanogen bromide digestion fragment that contains the negative regulatory residue Tyr 505 , and the identity of this site of phosphorylation was confirmed by trypsin digestion followed by high performance liquid chromatography . ^^^ Previous analyses have suggested that the CD 45 tyrosine phosphatase activates src family tyrosine kinases p56lck and p59fyn by dephosphorylating regulatory COOH terminal residues . ^^^ We have examined the status of p56lck and p59fyn in murine and human CD 45 T cell lines . ^^^ Surprisingly , despite the fact that p56lck and p59fyn were spontaneously hyperphosphorylated , the tyrosine kinase activity of both enzymes was increased in CD 45 versus CD45+ cells . ^^^ In vitro exposure of hyperphosphorylated p56lck to CD 45 decreased enzyme activity to near basal levels . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
HPTP beta shows distinctions from the related LAR PTPase and T cell CD 45 PTPase domains : it recognizes phosphotyrosyl peptides of 9 11 residues from lck , src , and PLC gamma with Km values of 2 , 4 , and 1 microM , some 40 200 fold lower than the other two PTPases . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 may positively regulate signaling by dephosphorylating the carboxyl terminal tyrosine of p56lck and p59fyn , and negatively regulate signaling by dephosphorylation of other TCR associated substrates directly . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 specifically modulates binding of Lck to a phosphopeptide encompassing the negative regulatory tyrosine of Lck . ^^^ Studies using CD 45 deficient cells have revealed that Lck , a tyrosine kinase thought to be essential for TCR signaling , is hyperphosphorylated on Y 505 in the absence of CD 45 . ^^^ Here we provide evidence that CD 45 can modulate the binding of the Lck to an 11 amino acid tyrosine phosphorylated peptide containing the carboxy terminus of Lck ( lckP ) . ^^^ Taken together , our data suggest that CD 45 specifically modulates the conformation of Lck in a manner consistent with the intramolecular model of regulation of Src like kinases . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Analysis of the CD 45 deficient CD8+ T cell clone L3M 93 demonstrates that the Src family members p56lck and p59fyn show increased immunoreactivity with anti phosphotyrosine antibody and exhibit decreased kinase activity . ^^^ Phosphorylation of the C terminal phosphopeptide , containing the negative regulatory site of tyrosine phosphorylation , from the CD 45 deficient cells was increased 8 fold for p56lck and 2 fold for p59fyn . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Differential effects of expression of the CD 45 tyrosine protein phosphatase on the tyrosine phosphorylation of the lck , fyn , and c src tyrosine protein kinases . ^^^ We have studied the phosphorylation of the closely related lck , fyn , and c src tyrosine protein kinases in leukemic murine T cell lines that have lost the expression of CD 45 . ^^^ The expression of CD 45 therefore regulates the phosphorylation and potentially the activity of the lck and fyn tyrosine protein kinases , but the effect on the lck kinase is much greater than on the fyn kinase . ^^^ Additionally , these findings are consistent with the hypothesis that the unresponsiveness of CD 45 negative lymphoid cells to antigenic stimulation is due largely to hyperphosphorylation of the lck kinase . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line . ^^^ One model to explain the role of CD 45 in regulating TCR signaling is that the phosphatase dephosphorylates the regulatory C terminal tyrosine of lck . ^^^ In the present report we confirm the finding of a trimolecular complex containing CD 45 , lck , and a 34 kDa protein ( p 34 ) in the Jurkat T cell line . ^^^ Additionally , we extend this work with the observation that specific in vitro kinase activity associated with CD 45 requires the expression of lck in Jurkat derived clones as does the in vivo phosphorylation of p 34 . ^^^ The association between CD 45 and lck is shown not to require the expression of or activation of the TCR . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Activation of MAP kinase / ERK occurred 3 fold less efficiently in a Jurkat line lacking functional p56lck ( JCAM . 1 ) , and was almost undetectable in a line lacking CD 45 ( J45 . 01 ) . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Fas ligation induces apoptosis and Jun kinase activation independently of CD 45 and Lck in human T cells . ^^^ It has been shown that TCR stimulation requires both the membrane tyrosine phosphatase , CD 45 , and the Src family kinase , Lck , to result in cellular activation . ^^^ Although prior studies suggest a role for protein tyrosine kinases and phosphatases in Fas signaling , we report here that Fas ligation induces apoptosis in T cells deficient in either CD 45 or Lck . ^^^ Further , in normal and CD 45 or Lck deficient cell lines , Fas stimulation results in activation of Jun kinase ( JNK ) , a proposed mediator of stress activation pathways . ^^^ Our data suggest that although CD 45 and Lck are not required for Fas signaling , JNK activation may play an important role transducing distal signals that lead to apoptosis after Fas ligation . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Signal transduction and glycophosphatidylinositol linked proteins ( lyn , lck , CD 4 , CD 45 , G proteins , and CD 55 ) selectively localize in Triton insoluble plasma membrane domains of human leukemic cell lines and normal granulocytes . ^^^ In the present study , we observed lck , lyn , src , hck , CD 4 , CD 45 , G proteins , and CD 55 ( decay accelerating factor ) expression in the buoyant low density Triton insoluble ( LDTI ) fraction of selected leukemic cell lines and granulocytes . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
A requirement for receptor mediated tyrosine kinase activity for ubiquitination was confirmed in cells lacking the tyrosine kinase p56lck and also in cells that are defective in expression of CD 45 , a tyrosine phosphatase that regulates the activity of p56lck . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
An activated epidermal growth factor receptor / Lck chimera restores early T cell receptor mediated calcium response in a CD 45 deficient T cell line . ^^^ Indirect evidence suggests that CD 45 function in TCR signaling involves the dephosphorylation of the C terminal negative regulatory site of p 56 ( lck ) , Tyr 505 . ^^^ To evaluate the importance of CD 45 mediated dephosphorylation of p 56 ( lck ) Tyr 505 in TCR signaling , we established CD 45 ( ) Jurkat cell lines expressing various forms of a chimera containing the extracellular and transmembrane domains of the epidermal growth factor receptor ( EGFR ) fused to p 56 ( lck ) . ^^^ We report that an activated EGFR / Lck chimera is able to reconstitute a Ca2+ response after CD 3 stimulation in the absence of CD 45 expression . ^^^ Altogether , these results provide the first direct evidence that the lack of efficient dephosphorylation of p 56 ( lck ) Tyr 505 is , in part , responsible for the unresponsiveness of CD 45 ( ) cells . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
We determined whether differences in phosphorylation between naive and proliferating T cells were due to altered regulation of p56lck ( Lck ) or p59fyn ( Fyn ) by their positive or negative regulators , CD 45 or p5Ocsk ( Csk ) , respectively . ^^^ Therefore , although the protein expression level of CD 45 was increased in proliferating T cells it only partially compensated for the hyperactivity of Csk resulting in a 2 fold reduction in the specific activity of Lck and Fyn in proliferating T cells . . ^^^
Interacting proteins: P08575 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 . ^^^ CD 45 dependent events such as tyrosine phosphorylation of Shc , activation of nuclear factor kappa B ( NF kappa B ) , activator protein 1 ( AP 1 ) , transcription factors , and stimulation of interleukin 2 ( IL 2 ) promoter and of CD 69 and CD 25 surface expression paralleled activation of the tyrosine kinases lck and fyn . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Mutational analysis of Lck in CD 45 negative T cells : dominant role of tyrosine 394 phosphorylation in kinase activity . ^^^ The CD 45 tyrosine phosphatase has been reported to activate the src family tyrosine kinases Lck and Fyn by dephosphorylating regulatory COOH terminal tyrosine residues 505 and 528 , respectively . ^^^ However , recent studies with CD 45 T cell lines have found that despite the fact that Lck and Fyn were constitutively hyperphosphorylated , the tyrosine kinase activity of both enzymes was actually increased . ^^^ In the present study , phosphoamino acid analysis revealed that the increased phosphorylation of Lck in CD 45 YAC 1 T cells was restricted to tyrosine residues . ^^^ To understand the relationship between tyrosine phosphorylation and Lck kinase activity , CD 45 YAC 1 cells were transfected with forms of Lck in which tyrosines whose phosphorylation is thought to regulate enzyme activity ( Tyr 192 , Tyr 394 , Tyr 505 , or both Tyr 394 and Tyr 505 ) were replaced with phenylalanine . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
In a CD4+ T helper cell dependent experimental autoimmune myocarditis model , we provide genetic evidence that cardiac myosin induced autoimmune myocarditis and the production of IgG auto Abs is dependent on functional T cells and did not occur in mice lacking the tyrosine kinase p56lck or the tyrosine phosphatase CD 45 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The common leukocyte antigen CD 45 plays a central role in T cell activation in coupling the T cell receptor ( TCR ) to the phosphatidylinositol pathway via interactions with TCR associated protein tyrosine kinases lck and fyn . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The Syk protein tyrosine kinase can function independently of CD 45 or Lck in T cell antigen receptor signaling . ^^^ The protein tyrosine phosphatase CD 45 is a critical component of the T cell antigen receptor ( TCR ) signaling pathway , acting as a positive regulator of Src family protein tyrosine kinases ( PTKs ) such as Lck . ^^^ 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: P08575 and P06239	Pubmed	SVM Score :0.0
Exclusion of CD 45 inhibits activity of p56lck associated with glycolipid enriched membrane domains . p56lck ( Lck ) is a lymphoid specific Src family tyrosine kinase that is critical for T cell development and activation . ^^^ Cells lacking CD 45 showed identical phosphorylation of Lck in GEM and TX 100 soluble membranes . ^^^ We propose that the GEM fraction represents a specific membrane domain present in T cells , and that the hyperphosphorylation of tyrosine and lower kinase activity of GEM associated Lck is due to exclusion of CD 45 from these domains . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Moreover , CD 45 coprecipitates with CD 4 molecules which are associated with Lck , as well as with those which are not associated with Lck . ^^^ Consistent with these observations and the role of CD 45 in the regulation of Lck function , effects on CD 4 associated membrane Lck are demonstrable . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
These effects do not correlate with changes in the expression of cell surface molecules implicated in antigen recognition , like TCR / CD3 , CD 2 , LFA 1 , or CD 45 , or with lower p56lck or p59fyn activity in the mutant cells . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
To investigate further the role of CD 45 in positive selection , we determined whether thymocytes that expressed a transgenic CD45RO molecule under the control of the proximal lck promoter can influence the positive selection of T cells in H Y TCR transgenic mice . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Optimal signal transduction through the T cell receptor ( TCR ) / CD3 complex requires the coordinated activities of protein tyrosine kinases ( PTKs ) Fyn and Lck in addition to protein tyrosine phosphatases ( PTPases ) such as CD 45 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
T cell receptor induced phosphorylation of Sos requires activity of CD 45 , Lck , and protein kinase C , but not ERK . ^^^ This requires expression of both the CD 45 tyrosine phosphatase and the Lck protein tyrosine kinase and depends upon signaling via protein kinase C . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
TR signaling was enhanced in a TCR negative Jurkat line and in T cell lines deficient in the tyrosine kinase lck or the tyrosine phosphatase CD 45 , both of which are essential for normal TCR function . ^^^
Interacting proteins: P08575 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: P08575 and P06239	Pubmed	SVM Score :0.0
Paxillin phosphorylation and association with Lck and Pyk 2 in anti CD 3 or anti CD 45 stimulated T cells . ^^^ Antibodies to either CD 3 or CD 45 have been shown to induce dramatic changes in cell morphology , increased tyrosine phosphorylation of cellular proteins , and the association of a subset of these proteins with the tyrosine kinase Lck . ^^^ The current study was initiated to determine the identity of the tyrosine phosphorylated 70 80 kDa protein that becomes Lck associated after stimulation with anti CD 45 or anti CD 3 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Biochemical analysis of the CD 45 p56 ( lck ) complex in Jurkat T cells lacking expression of lymphocyte phosphatase associated phosphoprotein . ^^^ In human and mouse lymphocytes the protein tyrosine phosphatase CD 45 , a key molecule involved in T cell activation , non covalently associates with the tyrosine kinase p 56 ( lck ) and lymphocyte phosphatase associated phosphoprotein ( LPAP ) , a 32 kDa phosphoprotein of unknown function . ^^^ Analysis of the CD 45 p56 ( lck ) molecular complex in this cell line revealed that loss of LPAP does not alter the expression or the enzymatic activity of CD 45 or p 56 ( lck ) . ^^^ In addition , the association between CD 45 and p 56 ( lck ) is not affected in LPAP deficient T cells . ^^^ These data suggest that LPAP does not regulate the enzymatic activity of CD 45 or p 56 ( lck ) and is not required for the association between these two proteins . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
RPTPalpha did not significantly alter the phosphorylation state or kinase activity of two CD 45 substrates , p 56 ( lck ) or p 59 ( fyn ) , suggesting that RPTPalpha does not have the same specificity or function as CD 45 in T cells . ^^^ Additional analysis with Src family phosphopeptides and recombinant p 56 ( lck ) as substrates indicated that CD 45 was consistently more active than RPTPalpha , having both higher Vmax and lower Km values . ^^^ Thus CD 45 is intrinsically a much more active phosphatase than RPTPalpha , which provides one reason why RPTPalpha can not effectively dephosphorylate p 56 ( lck ) and substitute for CD 45 in T cells . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Moreover , reconstitution of J45 . 01 and JCaM 1 cell lines with either CD 45 or Lck is accompanied by restoration of a normal thrombin induced [ Ca2+ ] 1 response and p38MAPK phosphorylation . ^^^ Here , we have analyzed p 42 44 MAPK , JNK and p 38 MAPK activation using Jurkat T cell lines deficient in either the tyrosine kinase p56Lck ( JCaM 1 ) or the tyrosine phosphatase CD 45 ( J45 . 01 ) . ^^^ Our results demonstrate that p56Lck and CD 45 exert a negative control on thrombin induced p 38 MAPK activation and [ Ca2+ ] 1 release in Jurkat cells . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Our results demonstrate for the first time an altered association of p56lck with coreceptors such as CD 4 and CD 45 in the elderly . ^^^ These results suggest that alterations in p56lck tyrosine kinase and its association with CD 4 and CD 45 may underlie lowered T cell function during aging . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Preliminary characterizations indicate that a PTP distinct from CD 45 , SHP 1 , and SHP 2 is present in T cell membranes and the inhibition of this yet unidentified PTP is most likely responsible for the Lck dependent tyrosine phosphorylation triggered by PTP inhibitors . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Furthermore , in contrast to ligand mediated TCR sorting , recycling of the TCR was independent of the tyrosine phosphatase CD 45 and the Src tyrosine kinases p 56 ( Lck ) and p 59 ( Fyn ) . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
MBCD released substantial quantities of GPI anchored Thy 1 and glycosphingolipid GM 1 , and also other surface proteins including CD 45 , and intracellular Lck and Fyn kinases . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
In vivo studies indicated that CD 3 induced HSI phosphorylation was dependent upon both the Src family tyrosine kinase Lck and the tyrosine phosphatase CD 45 , did not require MEK 1 kinase activity , and was regulated by protein kinase C activation . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Proper function of the protein tyrosine phosphatase CD 45 is required for the positive regulation of the activity of src tyrosine kinases p56lck and p59fyn which participate in T cell receptor and CD 4 receptor signalling . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
A central role for lck activity in determining the threshold for differentiation of the CD 4 lineage is revealed in experiments with thymi deficient for a regulator of lck activity , CD 45 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
In contrast , the SDF 1 responses of Jurkat clones with deficiencies in key TCR signaling components ( Lck , CD 45 , and TCR beta ) , were only marginally reduced by anti CD 3 stimulation . ^^^
Interacting proteins: P08575 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: P08575 and P06239	Pubmed	SVM Score :0.0
In this report we demonstrate that , in addition to the downregulation of TCR , CD 45 , and Lck ( which are key components of T cell activation ) , HTLV 1 infected cell lines demonstrate a large increase of FynB , a Fyn isoform usually poorly expressed in T cells . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The inhibitory mechanism acting on Lck and Fyn kinases in these membranes was independent of the protein tyrosine phosphatase CD 45 and was characterized as a mixed , noncompetitive one . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Expression of the p 56 ( Lck ) Y505F mutation in CD 45 deficient mice rescues thymocyte development . ^^^ To determine whether the block in thymocyte development was due to the inability to dephosphorylate the inhibitory phosphorylation site ( Y 505 ) in p 56 ( lck ) ( Lck ) , we generated CD 45 deficient mice that express transgenes for the Lck Y505F mutation and the DO11 . 10 T cell antigen receptor ( TCR ) . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 47 mediated cell death was independent of CD 3 , CD 4 , CD 45 , or p56lck involvement as demonstrated by studies with variant Jurkat cell lines deficient in these signaling pathways . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Although increases in intracellular calcium have been shown to modulate CD 45 activity , phosphorylation of p 56 ( Lck ) was not mediated via CD 45 . ^^^ Ionomycin stimulation of J 45 . 01 cells , a CD 45 negative Jurkat cell derivative , also resulted in p 56 ( Lck ) mobility shifts . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The CD 45 tyrosine phosphatase regulates CD 3 induced signal transduction and T cell development in recombinase deficient mice : restoration of pre TCR function by active p 56 ( lck ) . ^^^ CD 45 ( / ) mice were also crossed with pLGFA mice expressing a constitutively active form of the lck tyrosine kinase which restored the DN to DP transition to near normal levels . ^^^ Our results are consistent with a model in which CD 45 activated p 56 ( lck ) is critical for pre TCR signal transduction . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The apoptotic program initiated by the inhibition of tyrosine phosphatases did not require the presence of the tyrosine kinase p56lck or phosphatase CD 45 , whereas Bcl 2 overexpression protected T cells from pervanadate induced cytochrome C release , caspase 8 cleavage and apoptosis . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Thus , our results indicate a mechanism whereby TCR engagement promotes aggregation of lipid rafts , which facilitates colocalization of LCK , LAT , and the TCR whilst excluding CD 45 , thereby triggering protein tyrosine phosphorylation . . ^^^
Interacting proteins: P08575 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: P08575 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: P08575 and P06239	Pubmed	SVM Score :0.0
We propose a model to explain the activating effects of Campath 1H in which CD 52 mAb cross linking causes the trapping of TCR polypeptides within molecular complexes at the cell surface , thereby inducing signals via the TCR by a process which depends on the CD 45 mediated regulation of the p 56 ( lck ) and p 59 ( fyn ) tyrosine kinases . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 domain 2 enhanced phosphatase activity of the first domain in the full length cytoplasmic domain protein , whereas a chimeric protein with the SH 2 domain of p 56 ( lck ) in place of the CD 45 C terminal region did not . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Second , CD 8 mediated cross linking of p56lck by multimeric Kd peptide complexes or by anti CD 8 Ab results in p56lck activation in rafts , from which the abundant phosphatase CD 45 is excluded . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 positively modulates T cell receptor ( TCR ) signaling by constitutively priming p56lck through the dephosphorylation of the C terminal negative regulatory phosphotyrosine site . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Development of T leukaemias in CD 45 tyrosine phosphatase deficient mutant lck mice . ^^^ The CD 45 tyrosine phosphatase lowers T cell antigen receptor signalling thresholds by its positive actions on p 56 ( lck ) tyrosine kinase function . ^^^ We now show that mice expressing active lck ( F 505 ) at non oncogenic levels develop aggressive thymic lymphomas on a CD 45 ( / ) background . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Previously conflicting results are reconciled in a model suggesting how CD 45 regulates the p 56 ( lck ) tyrosine kinase in T cell signalling and development . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Similar to transmembrane PTP , CD 45 , the membrane associated populations of SHP 1 and SHP 2 are essentially excluded from lipid rafts , where other signaling molecules such as Lck , linker for activation of T cells , and CD 3 zeta are enriched . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 is a widely distributed phosphatase which modulates the activity of Lck by controlling the phosphorylation status of two tyrosine residues localized in the catalytic activation loop and in the negative regulatory domain . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Using RT PCR , we found that both species of the alternatively spliced mRNA for Pyk 2 were present in all of the lines regardless of their ability to express CD 45 or p 56 ( Lck ) protein . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Confocal microscopy demonstrated that colocalization of Lck and CD 45 was induced after restimulation with TSST 1 in APB CD4+ T cell blasts but not in thymic CD4+ T cell blasts . ^^^ These data indicate that interaction between Lck and CD 45 is suppressed physically in thymic CD4+ T cell blasts and plays a critical role in sustaining an anergic state . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 99 mediated death signaling proceeded independently of functional CD 3 , CD 4 , CD 45 , and p 56 ( lck ) , revealed distinctions from CD 47 mediated T cell death responses , and was not influenced by interference with CD 47 signaling . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 is a leukocyte specific protein tyrosine phosphatase that dephosphorylates the Src family kinases , Lck and Fyn , in T cells . ^^^ Positive regulation of Lck by CD 45 is required for its effective participation in T cell receptor signaling events . ^^^ Furthermore , 2 fold more Lck associated with CD 44 in the low density sucrose fraction from CD 45 ( ) T cells compared with CD 45 ( + ) T cells , suggesting that CD 45 may regulate the association of Lck with CD 44 in this fraction . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The tyrosine kinase and Ca ( 2+ ) independent mechanism was confirmed by comparing the H2O2 induced and the CD 3 induced inhibition of phosphatidylserine synthesis using several Jurkat clones differing in the expression of cell surface receptors such as CD3 / TCR and CD 45 and protein tyrosine kinase such as p72syk , ZAP 70 and p56lck . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Two mucin type glycoproteins , MUC 1 and P selectin glycoprotein ligand 1 ( PSGL 1 ) , and glycosphingolipids ( GSLs ) , expressed in human T cell line HUT 78 , were highly enriched in low density buoyant fraction ( termed `` GEM ' ' ) , together with CD 45 , Yes , Fyn , and lck ( 56 ) . ^^^
Interacting proteins: P08575 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: P08575 and P06239	Pubmed	SVM Score :0.0
Differential association of CD 45 isoforms with CD 4 and CD 8 regulates the actions of specific pools of p56lck tyrosine kinase in T cell antigen receptor signal transduction . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Anti CD 45 isoform antibodies enhance phagocytosis and gene expression of IL 8 and TNF alpha in human neutrophils by differential suppression on protein tyrosine phosphorylation and p56lck tyrosine kinase . ^^^ These results suggest that the cross linking of CD 45 isoforms by their specific antibodies stimulated different PMN activities by differential suppression on protein tyrosine phosphorylation and Src family tyrosine kinase p56lck . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
To test the importance of CD 45 exclusion from lipid microdomains for proper TCR signaling , a chimeric molecule was generated by fusing the CD 45 cytoplasmic region , which contains the PTP domains , to the amino terminal 12 amino acids of Lck , which target Lck to lipid microdomains . ^^^ Using 3A9 T lymphocyte hybridoma ( 3A9H ) cells whose TCR recognizes hen egg white lysozyme ( HEL ) , Lck CD 45 expression resulted in its targeting to lipid microdomains . ^^^ The 3A9H cells expressing Lck CD 45 were reduced in their responses to HEL or co cross linking of CD 3 and CD 4 , as assessed by IL 2 production and Ca ( 2+ ) mobilization . ^^^
Interacting proteins: P08575 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: P08575 and P06239	Pubmed	SVM Score :0.0
Substrates of CD 45 include the protein tyrosine kinases p 56 ( lck ) and p 59 ( fyn ) , both of which have been shown to be enriched in detergent insoluble microdomains . ^^^ Our data suggest that CD 45 is present in lipid rafts in T cells before activation , perhaps to activate raft associated p 56 ( lck ) , allowing membrane proximal signaling events to proceed . ^^^ Furthermore , the reduction in CD 45 content of lipid rafts after CD 3 stimulation may serve to limit the amounts of activated p 56 ( lck ) in rafts and thus possibly the duration of T cell responses . . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Confocal fluorescence microscopy shows that Lck colocalizes in rafts with GPI linked proteins , the adaptor protein LAT and Ras , but not with non raft membrane proteins including the protein tyrosine phosphatase CD 45 . ^^^ The TCR also associates with lipid rafts and its cross linking causes coaggregation of raft associated proteins including Lck , but not of CD 45 . ^^^ Our results indicate a mechanism whereby TCR engagement promotes aggregation of lipid rafts , which facilitates colocalization of signaling proteins including Lck , LAT , and the TCR , while excluding CD 45 , thereby potentiating protein tyrosine phosphorylation and downstream signaling . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
CD 45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR signaling . ^^^ The transmembrane phosphatase CD 45 regulates both Lck activity and T cell receptor ( TCR ) signaling . ^^^ Both basal Lck activity in unstimulated cells and the TCR induced increase in tyrosine phosphorylation of the TCR zeta chain and in Lck activity depend on the expression of CD 45 with a large ectodomain . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
It appeared that CD3 / TCR was constitutively associated with and recruited to a raft derived membrane subset because ( 1 ) all three membrane preparations contained a similar amount of the raft marker tyrosine kinase Lck but no detectable amounts of the conventional membrane markers , CD 45 phosphatase and transferrin receptor ; ( 2 ) a larger amount of particulate membranes were resistant to solubilization with 0 . 2 % Triton 10 100 and Brij 58 than to solubilization with 1 % Triton 10 100 ; and ( 3 ) higher cholesterol levels were present in membranes resistant to either the lower Triton 10 100 concentration or to Brij 58 , as compared with those resistant to 1 % Triton 10 100 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Using a combination of genetic and pharmacological approaches , we show herein that integrin signaling to Shc in T cells requires the receptor tyrosine phosphatase CD 45 , the Src family kinase member Lck , and protein kinase C . ^^^ Serine phosphorylation of Lck is dependent on PKC and is also linked to CD 45 dephosphorylation . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Transferrin receptor and the CD 45 tyrosine phosphatase did not colocalise with CT B GM 1 patches , whereas the tyrosine kinase Lck , the scaffolding protein LAT , and endogenous Ras proteins did partially colocalise with CT B GM 1 patches as did transfected EGFP K Ras ( 4B ) and EGFP H Ras . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The noncatalytic domains of Lck regulate its dephosphorylation by CD 45 . ^^^ The Src family tyrosine kinase , Lck , contains two key regulatory phosphotyrosine residues , tyrosine 394 ( Tyr 394 ) and tyrosine 505 ( Tyr 505 ) , both of which can be dephosphorylated by CD 45 . ^^^ Here , the interaction of CD 45 with its substrate , Lck , was determined to be complex , involving multiple interactions with both the catalytic and noncatalytic regions of Lck . ^^^ CD 45 preferentially dephosphorylated Tyr 394 over Tyr 505 in Lck . ^^^ The interactions with the noncatalytic domains of Lck and CD 45 enhanced the dephosphorylation of Tyr 394 whereas intramolecular interactions within Lck reduced , but did not abolish , the dephosphorylation of Tyr 505 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
The protein tyrosine kinases p 56 ( lck ) and the transmembrane tyrosine phosphatase CD 45 were all found to be involved in TCR CD 28 PGE ( 2 ) directed increase in HTLV 1 LTR activity . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Subdomain 10 of the kinase domain of Lck binds CD 45 and facilitates dephosphorylation . ^^^ The Src family kinase , Lck , is a major CD 45 substrate in T cells and CD 45 dephosphorylation of Lck is important for both T cell development and activation . ^^^ Analysis of the interaction between the cytoplasmic domain of CD 45 and its substrate , Lck , revealed that the active , membrane proximal phosphatase domain of CD 45 ( CD 45 D1 ) bound to the phosphorylated Lck kinase domain , the SH 2 domain , and the unique N terminal region of Lck . ^^^ The second , inactive phosphatase domain ( CD 45 D2 ) bound only to the kinase domain of Lck . ^^^ CD 45 D2 was unable to bind phosphotyrosine , and its interaction with the kinase domain of Lck was independent of tyrosine phosphorylation . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Besides the components of the CD 4 receptor complex , CD 4 and lck , we have identified by tandem mass spectrometry 17 tryptic peptides from transferrin receptor CD 71 , three peptides from protein phosphatase CD 45 , and one peptide from 4F2 lymphocyte activation antigen CD 98 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Additional unique oncogenic signals occur in pretumorigenic CD 45 ( / ) p 56 ( lck F505Y ) thymocytes in which p56lck kinase activity is 2 to 3 fold higher relative to p 56 ( lck F505Y ) : inhibition of DNA repair , inhibition of DNA damage induced Bcl XL deamidation , Bax conformational change and mitochondrial translocation , cytochrome c release , and the apoptotic caspase execution cascade . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
This study investigated the expression of molecules that regulate LCK homeostasis , such as CD 45 , C terminal Src kinase ( CSK ) , and c Cbl , in lipid raft domains from SLE T cells and investigated the localization of these proteins during T cell receptor ( TCR ) triggering . ^^^ Our results indicate that the expression of raft associated ganglioside , GM 1 , is increased in T cells from SLE patients and LCK may be differentially regulated due to an alteration in the association of CD 45 with lipid raft domains . ^^^ CD 45 tyrosine phosphatase , which regulates LCK activity , was differentially expressed and its localization into lipid rafts was increased in T cells from patients with SLE . ^^^ Furthermore , T cells allowed to `` rest ' ' in vitro showed a reversal of the changes in LCK , CD 45 , and GM 1 expression . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Studies with Jurkat cells deficient in Lck and CD 45 demonstrate that movement of CD 28 into lipid rafts does not require Lck and CD 45 and can occur despite reduction of CD 28 tyrosine phosphorylation to below the levels of detection . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
These results also demonstrate changes in the function and localization of critical signalling molecules such as the LCK tyrosine kinase and the CD 45 tyrosine phosphatase . . ^^^
Interacting proteins: P08575 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 . ^^^
Interacting proteins: P08575 and P06239	Pubmed	SVM Score :0.0
Expression of CD 45 lacking the catalytic protein tyrosine phosphatase domain modulates Lck phosphorylation and T cell activation . ^^^ In CD 45 Jurkat T cells , CD45RABC D 2 associated with Lck but , unlike its active counterpart CD45RABC , did not restore the induction of tyrosine phosphorylation or CD 69 expression upon T cell receptor ( TCR ) stimulation . ^^^ This indicates that the non catalytic domains of CD 45 can interact with Lck in T cells . ^^^ This finding suggests that , in addition to their established roles in the initiation of TCR signaling , CD 45 and Lck may also influence the type of TCR signal generated . . ^^^
Interacting proteins: P08575 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: P08575 and P06239	Pubmed	SVM Score :0.0
Through genetic dissection strategies , we have identified that the acquired immune system is activated through the T cell receptor and signaling amplification systems , such as the tyrosine kinase p56lck , phosphatase CD 45 and downstream ERK1 / 2 , and the family of cytokines . ^^^