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doi: 10.1242/10.1242/jcs.00109
Research Article |
1 The Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA
2 Department of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
* Author for correspondence (e-mail: laflams{at}mail.amc.edu)
Accepted 21 August 2002
Rac1 is a small Rho family GTPase that regulates changes in cell morphology associated with cell spreading and migration. Integrin-mediated adhesion is known to activate Rac1 and to regulate the interaction of Rac1 with downstream effectors. Currently, it is not clear how integrins signal Rac1 activation following cell adhesion. Integrin ß cytoplasmic domains (ß-tails) are known to be required for integrin-mediated cell spreading, and isolated ß tails expressed as tac-ß tail chimeras can inhibit cell spreading indicating that protein interactions with ß tails can regulate this process. Our recent studies demonstrated that the expression of constitutively activated Rac1 can restore cell spreading inhibited by tac ß tail chimeras, suggesting a role for Rac1 in the regulation of cell spreading by ß tails. Hence, we examined the role of ß tails in integrin activation of Rac1. By using recombinant wild-type and mutant integrin heterodimers, we demonstrate that integrin ß tails are required for adhesion to increase Rac1-GTP loading. We demonstrate that clustering tac-ß tail chimeras, on the surface of cells in suspension, activates Rac1. Thus, ß tails are not only required, but also sufficient for integrin-triggered Rac1 activation. Our findings indicate that integrin ß-tails are an important link between integrin engagement and Rac1 signaling, and that protein interactions initiated at ß tails are sufficient for integrins to regulate Rac1 activity.
Key words: Rac, Integrin, ß cytoplasmic domain
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