Related Experiment Video
Updated: Jul 31, 2026

RhoC GTPase Activation Assay
Published on: August 23, 2010
Protein kinase A regulates Rac and is required for the growth factor-stimulated migration of carcinoma cells
1Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
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.
Related Concept Videos
The Ras Gene
Ras is a superfamily...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Cell Polarization by Rho Proteins
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
MAPK Signaling Cascades
PI3K/mTOR/AKT Signaling Pathway

