Adhesion to ECM is required for many cell functions including cytoskel
etal organization, migration, and proliferation. We observed that when
cells first adhere to extracellular matrix, they spread rapidly by ex
tending filopodia-like projections and lamellipodia. These structures
are similar to the Rac- and Cdc42-dependent structures observed in gro
wth factor-stimulated cells. We therefore investigated the involvement
of Rac- and Cdc42 in adhesion and spreading on the ECM protein fibron
ectin. We found that integrin-dependent adhesion led to the rapid acti
vation of p21-activated kinase, a downstream effector of Cdc42 and Rac
, suggesting that integrins activate at least one of these GTPases. Do
minant negative mutants of Rac and Cdc42 inhibit cell spreading in suc
h a way as to suggest that integrins activate Cdc42, which leads to th
e subsequent activation of Rac; both GTPases then contribute to cell s
preading. These results demonstrate that initial integrin-dependent ac
tivation of Rac and Cdc42 mediates cell spreading.