Heparin inhibits mitogen-activated protein kinase activation in intact rat vascular smooth muscle cells.
Heparin is potently antiproliferative for vascular smooth muscle cells in vivo and in vitro, inhibiting early proto-oncogene expression and blocking proliferation in the G1 phase of the cell cycle. The mitogen-activated protein kinase (MAPK) family of serine- and threonine-specific kinases is activated in response to a wide range of mitogenic and other factors and is a key intermediate in cell signaling. We found that heparin inhibits activation of MAPK in response to fetal calf serum and phorbol 12-myristate 13-acetate, but not epidermal growth factor, revealing heparin-sensitive and -insensitive pathways of MAPK activation. This report tentatively links suppression of early proto-oncogene expression and inhibition of cellular proliferation by heparin with inhibition of a mitogenically relevant kinase in living cells.
Ottlinger
M E
ME
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Pukac
L A
LA
Karnovsky
M J
MJ
D000818:Animals; D001011:Aorta / Q000201:enzymology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D015151:Immunoblotting; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D004676:Myelin Basic Protein / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004676:Myelin Basic Protein; D047428:Protein Kinase Inhibitors; D004815:Epidermal Growth Factor; D006493:Heparin; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate