Crosstalk between protein kinase A and growth factor receptor signaling pathways in arterial smooth muscle

Crosstalk between the cyclic AMP-dependent protein kinase (PKA) and growth factor receptor signaling is one of many emerging concepts of crosstalk in signal transduction. Understanding of PKA crosstalk may have important impl ications for studies of crosstalk between other, less well known, signaling pathways. This review focuses on PKA crosstalk in arterial smooth muscle. Proliferation and migration of arterial smooth muscle cells (SMCs) contribu te to the thickening of the blood vessel wall that occurs in many types of cardiovascular disease. PKA potently inhibits SMC proliferation by antagoni zing the major mitogenic signaling pathways induced by growth factors in SM Cs. PKA also inhibits growth factor-induced SMC migration. An intricate cro sstalk between PKA and the mitogen activated protein kinase (MAPK/ERK) path way, the p70 S6 kinase pathway and cyclin-dependent kinases has been descri bed. Further, PKA regulates expression of growth regulatory molecules. The result of PKA activation in SMCs is the potent inhibition of cell cycle tra verse and SMC migration. In this review, we discuss recent advances iri our understanding of the crosstalk between PKA and signaling pathways induced by growth factor receptors in SMCs, and where relevant, in other cell types in which interesting examples of PKA, crosstalk have been described. (C) 1 999 Elsevier Science Inc.