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

The RAS quanine nucleotide binding proteins activate multiple signaling events that regulate cell growth and differentiation. In quiescent fibroblasts, ectopic expression of, activated H-RAS (H-[RAS.sup.V12], where V12 indicates valine-12) induces membrane ruffling, mitogen-activated protein (MAP) k...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1996-02, Vol.271 (5250), p.810
Main Authors: Joneson, Tom, White, Michael A, Wigler, Michael, Bar-Sagi, Dafna
Format: Article
Language:English
Subjects:
G proteins
Protein kinases
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Summary:The RAS quanine nucleotide binding proteins activate multiple signaling events that regulate cell growth and differentiation. In quiescent fibroblasts, ectopic expression of, activated H-RAS (H-[RAS.sup.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.sup.V12C4O] (where C40 indicates cysteine-40), was identified that was defective for MAP kinase activation and stimulation of DNA synthesis, but retained the ability to induce membrane ruffling. Another mutant of activated H-RAS, H-[RAS.sup.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 induced by H-[RAS.sup.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.
ISSN:0036-8075
1095-9203