Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase

Ally-Khan Somani, Jerome S. Bignon, Gordon B. Mills, Katherine A. Siminovitch, Donald R. Branch

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Activation of the cellular Src tyrosine kinase depends upon dephosphorylation of the carboxyl-terminal inhibitory tyrosine phosphorylation site. Herein we show that Src isolated from human platelets and Jurkat T cells is preferentially dephosphorylated at its inhibitory phosphotyrosine site by the SHP-1 tyrosine phosphatase. The data also revealed association of Src with SHP-1 in both platelets and lymphocytes and the capacity of Src to phosphorylate SHP-1 and interact with the SHP-1 NH2- terminal SH2 domain in vitro. Analysis of Src activity in thymocytes from SHP-1-deficient motheaten and viable motheaten mice revealed this kinase activity to be substantially lower than that detected in wild-type thymocytes, but to be enhanced by in vitro exposure to SHP-1. Similarly, immunoblotting analysis of thymocyte Src expression before and after selective depletion of active Src protein indicated that the proportion of active relative to inactive Src protein is markedly reduced in motheaten compared with wild-type cells. These observations, together with the finding of reduced Src activity in HEY cells expressing a dominant negative form of SHP-1, provide compelling evidence that SHP-1 functions include the positive regulation of Src activation.

Original languageEnglish (US)
Pages (from-to)21113-21119
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number34
DOIs
StatePublished - Aug 22 1997
Externally publishedYes

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Non-Receptor Type 6 Protein Tyrosine Phosphatase
src-Family Kinases
Thymocytes
Platelets
Chemical activation
Phosphotyrosine
Phosphorylation
T-cells
Lymphocytes
Blood Platelets
Tyrosine
Proteins
Jurkat Cells
Phosphotransferases
src Homology Domains
Cells
Association reactions
Immunoblotting
T-Lymphocytes
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase. / Somani, Ally-Khan; Bignon, Jerome S.; Mills, Gordon B.; Siminovitch, Katherine A.; Branch, Donald R.

In: Journal of Biological Chemistry, Vol. 272, No. 34, 22.08.1997, p. 21113-21119.

Research output: Contribution to journalArticle

Somani, Ally-Khan ; Bignon, Jerome S. ; Mills, Gordon B. ; Siminovitch, Katherine A. ; Branch, Donald R. / Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 34. pp. 21113-21119.
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