Activin A and TGF-beta stimulate phosphorylation of focal adhesion proteins and cytoskeletal reorganization in rat aortic smooth muscle cells

Activin A and Transforming Growth Factor-beta (TGF-beta) are members of a c ommon family of cytokines that bind to and stimulate serine/threonine kinas e receptors. Activin A and TGF-beta are important during embryonic developm ent exerting both positive and negative effects on cell growth. In the adul t organism, they function in processes such as tissue repair, cellular prol iferation, and differentiation. Although activin A and TGF-beta often induc e opposite functional outcomes in specific cells; proliferation or differen tiation, both were found to stimulate the. formation of actin stress fibers and focal adhesions in serum-starved rat aortic smooth muscle (RASM) cells , These structural changes were accompanied by phosphorylation of the focal adhesion proteins, paxillin, and p130(cas). Similar cytoskeletal and bioch emical changes were observed with the vasoactive agonist angiotensin II. Ac tivation of the ERK/MAP kinase pathway has been implicated in the migration in certain cell types, However, while activin A, TGF-beta, and angiotensin II all stimulated ERK activity in RASM cells, only activin A and angiotens in II stimulated migration. TGF-beta failed to illicit a chemotactic respon se. Furthermore,pharmacologic inhibition of MEK activity failed to block mi gration in response to activin A and angiotensin II, indicating RASM migrat ion can occur independent of ERK activity. These results suggest that TGF-b eta and activin A share several signaling pathways with angiotensin II lead ing to cytoskeletal remodeling and ERK activation, but there are distinct d ifferences regarding the effect of these agonists on cellular migration. (C ) 1999 Academic Press.