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Regulation of SHP-1 tyrosine phosphatase in human platelets by serine phosphorylation at its C terminus

Jones, M. L., Craik, J. D., Gibbins, J. M. and Poole, A. W. (2004) Regulation of SHP-1 tyrosine phosphatase in human platelets by serine phosphorylation at its C terminus. The Journal of Biological Chemistry, 279 (39). pp. 40475-40483. ISSN 1083-351X

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To link to this article DOI: 10.1074/jbc.M402970200

Abstract/Summary

SHP-1 is a Src homology 2 (SH2) domain-containing tyrosine phosphatase that plays an essential role in negative regulation of immune cell activity. We describe here a new model for regulation of SHP-1 involving phosphorylation of its C-terminal Ser(591) by associated protein kinase Calpha. In human platelets, SHP-1 was found to constitutively associate with its substrate Vav1 and, through its SH2 domains, with protein kinase Calpha. Upon activation of either PAR1 or PAR4 thrombin receptors, the association between the three proteins was retained, and Vav1 became phosphorylated on tyrosine and SHP-1 became phosphorylated on Ser(591). Phosphorylation of SHP-1 was mediated by protein kinase C and negatively regulated the activity of SHP-1 as demonstrated by a decrease in the in vitro ability of SHP-1 to dephosphorylate Vav1 on tyrosine. Protein kinase Calpha therefore critically and negatively regulates SHP-1 function, forming part of a mechanism to retain SHP-1 in a basal active state through interaction with its SH2 domains, and phosphorylating its C-terminal Ser(591) upon cellular activation leading to inhibition of SHP-1 activity and an increase in the tyrosine phosphorylation status of its substrates.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences
ID Code:10538
Uncontrolled Keywords:PROTEIN-KINASE-C, HEMATOPOIETIC-CELL PHOSPHATASE, SRC HOMOLOGY-2, DOMAINS, THROMBIN RECEPTOR, NEGATIVE REGULATION, CRYSTAL-STRUCTURE, T-CELLS, ACTIVATION, SH-PTP1, ASSOCIATION
Additional Information:The full text of this article is freely available via Pubmed using the link supplied below at Related URLs.
Publisher:American Society for Biochemistry and Molecular Biology

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