| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.68433317 |
| The variants encoded by the two alleles , 1858C and 1858T , differ in a crucial amino acid residue involved in association of LYP with the negative regulatory kinase Csk . 0.68433317^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.78170917 |
| The results of our experiments demonstrated that Csk physically associates with PEP , a protein tyrosine phosphatase ( PTP ) expressed in hemopoietic cells . 0.78170917^^^ The association between Csk and PEP was documented in transiently transfected Cos 1 cells and in a variety of cells of hemopoietic lineages , including T cells . 0.62940703^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| Here we report the association of RA susceptibility with the minor allele of a missense SNP in PTPN 22 ( discovery study allelic P=6 . 6 10 10 ( 4 ) ; replication study allelic P=5 . 6 10 10 ( 8 ) ) , which encodes a hematopoietic specific protein tyrosine phosphatase also known as `` Lyp . ' ' We show that the risk allele , which is present in approximately 17 % of white individuals from the general population and in approximately 28 % of white individuals with RA , disrupts the P 1 proline rich motif that is important for interaction with Csk , potentially altering these proteins ' normal function as negative regulators of T cell activation . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| One function of Lyp is downregulation of T cell signaling through its interaction with the negative regulatory kinase C terminal Src tyrosine kinase ( Csk ) . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| The lymphoid specific phosphatase ( LYP ) encoded by PTPN 22 is involved in preventing spontaneous T cell activation by dephosphorylating and inactivating T cell receptor associated Csk kinase . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| Lyp is expressed in lymphocytes , where it physically associates through its proline rich motif ( called P 1 ) with the SH 3 domain of the protein tyrosine kinase Csk , an important suppressor of the Src family of kinases Lck and Fyn , which mediate TCR signaling . ^^^ Therefore , it is said that interaction between Lyp and Csk enables these effectors to inhibit T cell activation synergistically . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| We previously demonstrated that , via its Src homology 3 ( SH 3 ) domain , Csk is tightly bound to PEP , a protein tyrosine phosphatase ( PTP ) exclusively expressed in hemopoietic cells . ^^^ In this report , we have tested the possibility that Csk also interacts with PTP PEST , a ubiquitous PTP sharing structural homology with PEP . ^^^ Even though both PTP PEST and PEP were associated with Csk , significant differences were noted between these two PTPs . ^^^ In combination , these findings indicated that , like PEP , PTP PEST is probably involved in Csk mediated functions in mammalian cells . ^^^ Moreover , they suggested that the roles of Csk PTP PEST and Csk PEP are likely to be different . . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| Sequence requirements for association of protein tyrosine phosphatase PEP with the Src homology 3 domain of inhibitory tyrosine protein kinase p 50 ( csk ) . ^^^ Previously , we reported that the inhibitory tyrosine protein kinase p 50 ( csk ) is physically associated with the protein tyrosine phosphatase PEP in hematopoietic cells . ^^^ This interaction was shown to involve the Src homology 3 ( SH 3 ) region of Csk and a proline rich sequence of PEP termed P 1 ( SRRTDDEIPPPLPERTPESFIVVEE ) . ^^^ Our studies revealed that the proline rich core of the P 1 region of PEP ( PPPLPERT ) was necessary but not sufficient for binding to p 50 ( csk ) . ^^^ In addition to clarifying the molecular basis for the selective ability of PEP to associate with Csk , these results constitute further evidence that sequences outside proline rich cores dictate the specificity of SH 3 domain mediated interactions in vivo . . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| Subsequent studies uncovered that , via its SH 3 domain , p 50 ( csk ) was associated with PEP , a proline enriched protein tyrosine phosphatase ( PTP ) of unknown function expressed in hemopoietic cells . ^^^ Herein , we have attempted to identify the role of the Csk PEP complex in T lymphocytes . ^^^ The results of our experiments showed that , like Csk , PEP was a strong repressor of TCR signaling . ^^^ This property was dependent on the phosphatase activity of PEP , as well as on the sequence mediating its binding to p 50 ( csk ) . ^^^ Through reconstitution experiments in Cos 1 cells , evidence was obtained that Csk and PEP act synergistically to inhibit protein tyrosine phosphorylation by Src related kinases , and that this effect requires their association . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| The proline , glutamic acid , serine and threonine enriched protein tyrosine phosphatase PEP , which is expressed primarily in hematopoietic cells , was recently discovered to be physically associated with the 50 kDa cytosolic protein tyrosine kinase ( PTK ) Csk , an important suppressor of Src family PTK , including Lck and Fyn in T cells . ^^^ Finally , we observed that PEP reduced c fos activation in a synergistic manner with Csk , supporting the notion that these two enzymes form a functional team acting on Src family kinases involved in TCR signaling . . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| We showed previously that the Csk SH 3 domain mediates highly specific associations with two members of the PEP family of nonreceptor protein tyrosine phosphatases ( PTPs ) , PEP and PTP PEST . ^^^ Using a modified yeast two hybrid screen , we uncovered the fact that Csk associates with PTP HSCF , the third member of the PEP family of PTPs . ^^^ Coupled with previously published observations , these data also establish that Csk forms complexes with all three known members of the PEP family . . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| C terminal Src kinase ( Csk ) takes part in a highly specific , high affinity interaction via its Src homology 3 ( SH 3 ) domain with the proline enriched tyrosine phosphatase PEP in hematopoietic cells . ^^^ The solution structure of the Csk SH 3 domain in complex with a 25 residue peptide from the Pro / Glu / Ser / Thr rich ( PEST ) domain of PEP reveals the basis for this specific peptide recognition motif involving an SH 3 domain . ^^^ Three residues , Ala 40 , Thr 42 and Lys 43 , in the SH 3 domain of Csk specifically recognize two hydrophobic residues , Ile 625 and Val 626 , in the proline rich sequence of the PEST domain of PEP . ^^^ This interaction is required in addition to the classic polyproline helix ( PPII ) recognition by the Csk SH 3 domain for the association between Csk and PEP in vivo . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| PEP is primarily expressed in hematopoietic cells , and together with PEP binding Csk , may act as a negative regulator of antigen receptor signaling in lymphocytes . ^^^ |
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| Interacting proteins: Q9Y2R2 and P41240 |
Pubmed |
SVM Score :0.0 |
| NA |
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