Title

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

UMMS Affiliation

Department of Cancer Biology

Date

10-19-2001

Document Type

Article

Subjects

Antigens, CD29; Breast Neoplasms; Chemotaxis; Cyclic AMP-Dependent Protein Kinases; Epidermal Growth Factor; Humans; Lysophospholipids; Signal Transduction; Tumor Cells, Cultured; rac GTP-Binding Proteins; rhoA GTP-Binding Protein

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.

Rights and Permissions

Citation: J Biol Chem. 2001 Dec 21;276(51):47895-900. Epub 2001 Oct 17. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

11606581