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J. Biol. Chem., Vol. 283, Issue 20, 13799-13805, May 16, 2008

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cAMP Inhibits Cell Migration by Interfering with Rac-induced Lamellipodium Formation^*

From the Department of Physiology, Cornell University Weill Medical College, New York, New York 10021

Cell migration is critical for animal development and physiological as well as pathological responses. One important step during cell migration is the formation of lamellipodia at the leading edge of migrating cells. Here we report that the second messenger cAMP inhibits the migration of mouse embryonic fibroblast cells and mouse breast tumor cells. cAMP acts downstream of the small GTPase Rac and interferes with the formation of lamellipodia. Moreover, cAMP decreases the phosphorylation of the myosin light chain at the leading edge of cells and increases the phosphorylation of the vasodilator-stimulated phosphoprotein. Together with our previous report of a positive role of another second messenger, cGMP, in lamellipodium formation, our data indicate that cAMP and cGMP play opposite roles in modulating lamellipodium formation.

Received for publication, January 23, 2008 , and in revised form, March 17, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant AG23202. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 212-746-6362; Fax: 212-746-8690; E-mail: xyhuang{at}med.cornell.edu.

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