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(Received for publication, February 6, 1997)
From the Department of Cell Biology and Physiology, Washington
University School of Medicine, St. Louis, Missouri 63110 and the
¶ Fred Hutchinson Cancer Research Center, Seattle, Washington
98104
Activation of Ras stimulates cell surface
membrane ruffling and pinocytosis. Although seen as coupled events, our
study demonstrates that membrane ruffling and pinocytosis are regulated
by distinct Ras signal transduction pathways. Ras controls membrane
ruffling via the small GTPase Rac. In BHK-21 cells, expression of the
constitutively active Rac1(G12V) mutant, via a Sindbis virus vector,
resulted in a dramatic stimulation of membrane ruffling without
affecting the uptake of horseradish peroxidase. Expression of
Ha-Ras(G12V), an activated Ras mutant, stimulated both membrane
ruffling and horseradish peroxidase uptake. The Ha-Ras(G12V)-stimulated
pinocytosis but not membrane ruffling was abolished by either
wortmannin or co-expression with a dominant negative mutant of Rab5,
Rab5(S34N). Expression of the activated Rab5(Q79L) mutant mimics the
stimulatory effect of Ha-Ras(G12V) on pinocytosis but not membrane
ruffling. Our data indicate that Ha-Ras(G12V) separately activates
Rab5-dependent pinocytosis and Rac1-dependent
membrane ruffling.
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