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.