Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav

Jaewon Han, Katherine J Phelps, Balaka Das, Xiaodong Shu, Yi Xia, Raymond D. Mosteller, U. Murali Krishna, J R Falck, Michael A White, Daniel Broek

Research output: Contribution to journalArticle

672 Scopus citations

Abstract

Mitogen stimulation of cytoskeletal changes and c-jun amino-terminal kinases is mediated by Rac small guanine nucleotide-binding proteins. Vav, a guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange factor for Rac that stimulates the exchange of bound GDP for GTP, bound to and was directly controlled by substrates and products of phosphoinositide (PI) 3- kinase. The PI 3-kinase substrate phosphatidylinositol-4,5-bisphosphate inhibited activation of Vav by the tyrosine kinase Lck, whereas the product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav by Lck. Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac.

Original languageEnglish (US)
Pages (from-to)558-560
Number of pages3
JournalScience
Volume279
Issue number5350
DOIs
StatePublished - Jan 23 1998

ASJC Scopus subject areas

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