Protein kinase A regulates Rac and is required for the growth factor-stimulated migration of carcinoma cells

The Journal of Biological Chemistry
K L O'Connor, A M Mercurio

Abstract

Members of the Rho family of small GTPases, such as Rho and Rac, are required for actin cytoskeletal reorganization during the migration of carcinoma cells. Phosphodiesterases are necessary for this migration because they alleviate cAMP-dependent protein kinase (PKA)-mediated inhibition of RhoA (O'Connor, K. L., Shaw, L. M., and Mercurio, A. M. (1998) J. Cell Biol. 143, 1749-1760; O'Connor K. L., Nguyen, B.-K., and Mercurio, A. M. (2000), J. Cell Biol. 148, 253-258). In this study, we report that the migration of breast and squamous carcinoma cells toward either lysophosphatidic acid or epidermal growth factor involves not only phosphodiesterase activity but also cooperative signaling from PKA. Furthermore, we demonstrate that Rac1 activation in response to chemoattractant or beta(1) integrin clustering is regulated by PKA and that Rac1 is required for this migration. Also, we find that beta(1) integrin signaling stimulates the rapid and transient activation of PKA. A novel implication of these findings is that carcinoma cell migration is controlled by cAMP-dependent as well as cAMP inhibitory signaling mechanisms.

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Citations

Sep 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Alan K HoweBrian P Hogan
Jan 12, 2005·Breast Cancer Research : BCR·Anupama E GururajRakesh Kumar
Sep 12, 2008·Molecular Biology of the Cell·Chinten J LimMark H Ginsberg
Sep 23, 2008·The Journal of Biological Chemistry·Annette M GonzalezJonathan C R Jones
Dec 25, 2008·The Journal of Biological Chemistry·Adriana A Paulucci-HolthauzenKathleen L O'Connor
Dec 2, 2010·The Journal of Biological Chemistry·Hiroshi YamashitaNoriyuki Kioka
Nov 4, 2011·American Journal of Physiology. Cell Physiology·Kathleen L O'ConnorL Nicole Towers
Jan 23, 2004·American Journal of Physiology. Endocrinology and Metabolism·Jingsong LiGuoDong Li
Jul 24, 2004·American Journal of Physiology. Heart and Circulatory Physiology·J WaschkeF E Curry
Aug 26, 2003·Journal of Cellular Biochemistry·J Brian NauertLinda B Lester
Jan 12, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Koji KobayashiTakahisa Murata
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