TRANSFORMING GROWTH-FACTOR-BETA - SIGNAL-TRANSDUCTION VIA PROTEIN-KINASE-C IN CULTURED EMBRYONIC VASCULAR SMOOTH-MUSCLE CELLS

Transforming growth factor-beta (TGF-beta), an ubiquitous regulatory p eptide, has diverse effects on the differentiation and behavior of vas cular smooth muscle cells (VSMC). However, the molecular mechanism thr ough which TGF-alpha exerts its effects remains obscure. We investigat ed the phosphoinositide/protein kinase C [PKC] signaling pathway in th e action of TGF-beta on cultured embryonic avian VSMC of differing lin eage: a) thoracic aorta, derived from the neural crest; and b) abdomin al aorta, derived from mesenchyme. The second messenger responsible fo r activation of PKC is sn-1,2-diacylglycerol [DAG]; TGF-beta increased the mass amounts of DAG in the membranes of neural crest-derived VSMC concurrent with translocation of PKC from the soluble to the membrane fraction, but TGF-beta had no effect on the DAG or PKC of mesenchyme- derived VSMC. TGF-beta potentiated the growth of platelet-derived grow th factor (PDGF)-treated, neural crest-derived VSMC; but abolished PDG F-induced growth of mesenchymal cells. It is concluded that molecular and functional responses of VSMC to TGF-beta are heterogeneous and are functions of the embryonic lineage of the VSMC.