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 common family of cytokines that bind to and stimulate serine/threonine kinase receptors. Activin A and TGF-beta are important during embryonic development exerting both positive and negative effects on cell growth. In the adult organism, they function in processes such as tissue repair, cellular proliferation, and differentiation. Although activin A and TGF-beta often induce opposite functional outcomes in specific cells; proliferation or differentiation, 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 biochemical changes were observed with the vasoactive agonist angiotensin II. Activation 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 angiotensin II stimulated migration. TGF-beta failed to illicit a chemotactic response. Furthermore, pharmacologic inhibition of MEK activity failed to block migration in response to activin A and angiotensin II, indicating RASM migration can occur independent of ERK activity. These results suggest that TGF-beta and activin A share several signaling pathways with angiotensin II leading to cytoskeletal remodeling and ERK activation, but there are distinct differences regarding the effect of these agonists on cellular migration.
Riedy
M C
MC
Program in Cell and Molecular Biology, State University of New York Health Science Center at Syracuse, 750 East Adams Street, Syracuse, New York 13210, USA.
Brown
M C
MC
Molloy
C J
CJ
Turner
C E
CE
D000199:Actins / Q000378:metabolism; D028341:Activins; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D007265:Inhibins / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011506:Proteins; D051381:Rats; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000199:Actins; C493843:Bcar1 protein, rat; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins; D051419:Paxillin; D010750:Phosphoproteins; D011506:Proteins; C496063:Pxn protein, rat; D050717:Retinoblastoma-Like Protein p130; D016212:Transforming Growth Factor beta; D028341:Activins; D000804:Angiotensin II; D007265:Inhibins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases