Protein Kinase A Regulates Rac and Is Required for the Growth Factor-stimulated Migration of Carcinoma Cells

Kathleen L. O'Connor, Arthur M. Mercurio

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

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 Racl activation in response to chemoattractant or β1 integrin clustering is regulated by PKA and that Rac1 is required for this migration. Also, we find that β1 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.

Original languageEnglish
Pages (from-to)47895-47900
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number51
DOIs
StatePublished - Dec 21 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Protein Kinase A Regulates Rac and Is Required for the Growth Factor-stimulated Migration of Carcinoma Cells'. Together they form a unique fingerprint.

Cite this