A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos

Jean Paul Olivier, Thomas Raabe, Mark Henkemeyer, Barry Dickson, Geraldine Mbamalu, Ben Margolis, Joseph Schlessinger, Ernst Hafen, Tony Pawson

Research output: Contribution to journalArticle

438 Scopus citations

Abstract

A Drosophila gene (drk) encodes a widely expressed protein with a single SH2 domain and two flanking SH3 domains, which is homologous to the Sem-5 protein of C. elegans and mammalian GRB2. Genetic analysis suggests that drk function is essential for signaling by the sevenless receptor tyrosine kinase. Drk biological activity correlates with binding of itS SH2 domain to activated receptor tyrosine kinases and concomitant localization of drk to the plasma membrane. In vitro, drk also binds directly to the C-terminal tall of Sos, a Ras guanine nucleotide-releasing protein (GNRP), which, like Ras1 and drk, is required for sevenless signaling. These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. The conservation of these signaling proteins during evolution indicates that this is a general mechanism for linking tyrosine kinases to Ras.

Original languageEnglish (US)
Pages (from-to)179-191
Number of pages13
JournalCell
Volume73
Issue number1
DOIs
StatePublished - Apr 9 1993

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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