Protein kinase A regulates Rac and is required for the growth factor-stimulated migration of carcinoma cells
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2001-10-19Keywords
Antigens, CD29Breast 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
Cancer Biology
Neoplasms
Metadata
Show full item recordAbstract
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.Source
J Biol Chem. 2001 Dec 21;276(51):47895-900. Epub 2001 Oct 17. Link to article on publisher's siteDOI
10.1074/jbc.M107235200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26284PubMed ID
11606581Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M107235200