Activation of S6 kinase in cultured vascular smooth muscle cells by submitogenic levels of thrombospondin.
Purified human platelet thrombospondin was shown to activate S6 kinase in cultured vascular smooth muscle cells in a dose- (1-9 micrograms/ml) and time-dependent manner. Down regulation of epidermal growth factor and somatomedin C receptors by prior treatment of cells with their respective growth factors did not reduce this effect. Kinase activation by thrombospondin was only marginally reduced in the presence of platelet-derived growth factor specific antibody at levels that totally inhibited platelet-derived growth factor (5 ng/ml) induced activation. Additionally, thrombospondin elicits a rapid dose-dependent phosphoinositide turnover response analogous to that of platelet-derived growth factor, epidermal growth factor and somatomedin C. Prior treatment of cells with phorbol ester for 48 hrs in serum-free culture medium resulted in a small enhancement of S6 kinase activation by thrombospondin and the above mentioned growth factors but a complete loss in the ability of phorbol ester to activate this enzyme. These findings with cultured smooth muscle cells suggest a growth factor-like role for thrombospondin.
Scott-Burden
T
T
Department of Research, University Hospital, Basel, Switzerland.
Resink
T J
TJ
Baur
U
U
Bürgin
M
M
Bühler
F R
FR
D000818:Animals; D000911:Antibodies, Monoclonal; D001013:Aorta, Thoracic / Q000201:enzymology; D001792:Blood Platelets / Q000032:analysis; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D008938:Mitosis / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D019893:Ribosomal Protein S6 Kinases; D019699:Thrombospondins
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D010982:Platelet-Derived Growth Factor; D019699:Thrombospondins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases