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 peptide, has diverse effects on the differentiation and behavior of vascular smooth muscle cells (VSMC). However, the molecular mechanism through which TGF-alpha exerts its effects remains obscure. We investigated the phosphoinositide/protein kinase C [PKC] signaling pathway in the action of TGF-beta on cultured embryonic avian VSMC of differing lineage: a) thoracic aorta, derived from the neural crest; and b) abdominal aorta, derived from mesenchyme. The second messenger responsible for 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 growth factor (PDGF)-treated, neural crest-derived VSMC; but abolished PDGF-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.
Wrenn
R W
RW
Department of Cellular Biology and Anatomy, School of Medicine, Medical College of Georgia, Augusta 30912.
Raeuber
C L
CL
Herman
L E
LE
Walton
W J
WJ
Rosenquist
T H
TH
D000818:Animals; D001012:Aorta, Abdominal; D001013:Aorta, Thoracic; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002642:Chick Embryo; D004075:Diglycerides / Q000032:analysis; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000196:embryology; D009432:Neural Crest / Q000187:drug effects / Q000502:physiology; D010982:Platelet-Derived Growth Factor; D011493:Protein Kinase C / Q000032:analysis*; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D004075:Diglycerides; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C