A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in Ras activation in T cells

L. Buday, Sean E. Egan, Pablo Rodriguez Viciana, Doreen A. Cantrell, Julian Downward

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

T lymphocytes contain both Grb2, an SH2 and SH3 domain containing adaptor protein, and Sos, a guanine nucleotide exchange factor for Ras. Immunoprecipitates of Sos from the lysates of T cells contain a 36-kDa protein which is phosphorylated on tyrosine residues in response to T cell receptor/CD3 cross-linking. In vitro studies using different bacterially synthesized GST-Sos fusion proteins confirm the formation of complexes containing p36 and the proline-rich COOH-terminal domain of Sos. The use of mutant GST-Grb2 proteins in which both SH3 domains have been mutationally inactivated shows that Grb2 binds to tyrosine phosphorylated p36 via its SH2 domain. In Jurkat cells phosphorylated p36 is localized exclusively in the particulate fraction. In addition, another SH2 domain-containing protein, p52(She) is tyrosine phosphorylated upon TCR-CD3 cross-linking and associates with a 150-kDa phosphotyrosine containing protein. Taken together these data suggest that activation of Ras in T cells via the TCR·CD3 complex might be controlled, at least in part, by mechanisms similar to those found in fibroblasts, involving in this case formation of a complex of Grb2, Sos, and a membrane-bound tyrosine phosphoprotein of molecular mass 36-kDa.

Original languageEnglish
Pages (from-to)9019-9023
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number12
Publication statusPublished - Mar 25 1994

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T-cells
Phosphoproteins
src Homology Domains
Tyrosine
Chemical activation
Membranes
T-Lymphocytes
Proteins
ras Guanine Nucleotide Exchange Factors
Phosphotyrosine
Jurkat Cells
Molecular mass
Fibroblasts
T-Cell Antigen Receptor
Proline
Fusion reactions

ASJC Scopus subject areas

  • Biochemistry

Cite this

A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in Ras activation in T cells. / Buday, L.; Egan, Sean E.; Viciana, Pablo Rodriguez; Cantrell, Doreen A.; Downward, Julian.

In: Journal of Biological Chemistry, Vol. 269, No. 12, 25.03.1994, p. 9019-9023.

Research output: Contribution to journalArticle

Buday, L. ; Egan, Sean E. ; Viciana, Pablo Rodriguez ; Cantrell, Doreen A. ; Downward, Julian. / A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in Ras activation in T cells. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 12. pp. 9019-9023.
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