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Activation of Rac and Cdc42 by integrins mediates cell spreading
L S Price1, J Leng, M A Schwartz
1Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Molecular Biology of the Cell
|July 11, 1998
Summary
Cell adhesion to the extracellular matrix (ECM) activates Rac and Cdc42 GTPases. These proteins are crucial for cell spreading, demonstrating integrin-dependent signaling in early cell functions.
Area of Science:
- Cell Biology
- Molecular Biology
Background:
- Cell adhesion to the extracellular matrix (ECM) is vital for cellular functions like migration and proliferation.
- Initial cell adhesion involves rapid spreading via filopodia and lamellipodia, resembling growth factor-induced structures.
Purpose of the Study:
- To investigate the roles of Rac and Cdc42 GTPases in cell adhesion and spreading on fibronectin.
- To determine if integrin-dependent adhesion activates Rac and Cdc42.
Main Methods:
- Utilizing dominant-negative mutants of Rac and Cdc42 to assess their impact on cell spreading.
- Monitoring the activation of p21-activated kinase (PAK) as an indicator of Rac/Cdc42 activity.
Main Results:
- Integrin-dependent adhesion rapidly activated p21-activated kinase (PAK), a downstream effector of Rac and Cdc42.
- Inhibition of Rac and Cdc42 function significantly impaired cell spreading.
- Evidence suggests integrins activate Cdc42, which subsequently activates Rac, both contributing to cell spreading.
Conclusions:
- Integrin-mediated cell adhesion initiates the activation of Cdc42 and Rac GTPases.
- The sequential activation of Cdc42 and Rac by integrins is a key mechanism driving initial cell spreading on the ECM.