title: Activation of S6 kinase in cultured vascular smooth muscle cells by submitogenic levels of thrombospondin.
abstract: 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.
authors.affiliation: Department of Research, University Hospital, Basel, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Scott-Burden
authors.forename: T J
authors.initials: TJ
authors.lastname: Resink
authors.forename: U
authors.initials: U
authors.lastname: Baur
authors.forename: M
authors.initials: M
authors.lastname: Bürgin
authors.forename: F R
authors.initials: FR
authors.lastname: Bühler
mesh_terms: 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
chemical_list: 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