TY - JOUR
T1 - Protein Kinase A Regulates Rac and Is Required for the Growth Factor-stimulated Migration of Carcinoma Cells
AU - O'Connor, Kathleen L.
AU - Mercurio, Arthur M.
PY - 2001/12/21
Y1 - 2001/12/21
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M107235200
DO - 10.1074/jbc.M107235200
M3 - Article
C2 - 11606581
AN - SCOPUS:0035930585
SN - 0021-9258
VL - 276
SP - 47895
EP - 47900
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 51
ER -