PKC-MEK-MAPK-dependent signal transduction pathway mediates the stimulation of lysyl oxidase expression by serum and PDGF in rat aortic smooth muscle cells.
Lysyl oxidase (LO) plays a critical role in the stabilization and insolubilization of fibrous structural proteins of the extracellular matrix and has been implicated in the suppression of Ras-induced tumorigenesis. Several prior reports demonstrate that the expression of this catalyst is strongly influenced by a variety of effectors of cell function and is responsive to the growth state of fibrogenic cells. Using specific inhibitors of components of signal transduction pathways, the present study reveals that a PKC-MEK-MAPK-dependent pathway is critical to the enhanced expression of the LO gene in response to variations in the levels of the serum component of the growth medium and in response to platelet-derived growth factor (PDGF). PDGF is shown to be the major component of fetal bovine serum, which stimulates the activity of a LO promoter construct.
Smith-Mungo
Lynda
L
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Kagan
Herbert M
HM
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D003470:Culture Media; D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D008249:Protein-Lysine 6-Oxidase; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases