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Vol. 9, Issue 7, 1863-1871, July 1998
and
Departments of
*Vascular Biology,
Adhesion to ECM is required for many cell functions including
cytoskeletal organization, migration, and proliferation. We observed
that when cells first adhere to extracellular matrix, they spread
rapidly by extending filopodia-like projections and lamellipodia. These
structures are similar to the Rac- and Cdc42-dependent structures
observed in growth factor-stimulated cells. We therefore investigated
the involvement of Rac and Cdc42 in adhesion and spreading on the ECM
protein fibronectin. We found that integrin-dependent adhesion
led to the rapid activation of p21-activated kinase, a downstream
effector of Cdc42 and Rac, suggesting that integrins activate
at least one of these GTPases. Dominant negative mutants of Rac and
Cdc42 inhibit cell spreading in such a way as to suggest that
integrins activate Cdc42, which leads to the subsequent
activation of Rac; both GTPases then contribute to cell spreading.
These results demonstrate that initial integrin-dependent
activation of Rac and Cdc42 mediates cell spreading.
Immunology, and
§Cell Biology, The Scripps Research Institute, La Jolla,
California 92037
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