Stimulation of membrane ruffling and MAP kinase activation by distinct effectors of RAS

Tom Joneson, Michael A. White, Michael H. Wigler, Dafna Bar-Sagi

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347 Scopus citations

Abstract

The RAS guanine nucleotide binding proteins activate multiple signalling events that regulate cell growth and differentiation. In quiescent fibroblasts, ectopic expression of activated H-RAS (H-RAS(V12), where V12 indicates valine-12) induces membrane ruffling, mitogen-activated protein (MAP) kinase activation, and stimulation of DNA synthesis. A mutant of activated H-RAS, H-RAS(V12C40) (where C40 indicates cysteine-40), was identified that was defective for MAP kinase activation and stimulation of DNA synthesis, but retained the ability to introduce membrane ruffling. Another mutant of activated H-RAS, H-RAS(V12S35) (where S35 indicates serine-35), which activates MAP kinase, was defective for stimulation of membrane ruffling and induction of DNA synthesis. Expression of both mutants resulted in a stimulation of DNA synthesis that was comparable to that of induced by H-RAS(V12). These results indicate that membrane ruffling and activation of MAP kinase represent distinct RAS effector pathways and that input from both pathways is required for the mitogenic activity of RAS.

Original languageEnglish (US)
Pages (from-to)810-812
Number of pages3
JournalScience
Volume271
Issue number5250
DOIs
StatePublished - Feb 9 1996

ASJC Scopus subject areas

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