Vascular smooth muscle cell-derived, Gla-containing growth-potentiating factor for Ca(2+)-mobilizing growth factors.
Proliferation of vascular smooth muscle cells (VSMC) is triggered by two types of growth factors. One activates tyrosine kinase-type receptors and the other activates G-protein-coupled receptors. We found that a conditioned medium of rat VSMC contained a growth-potentiating activity for the latter type of growth factor, and we purified a 70-kDa growth-potentiating factor (GPF) from the conditioned medium. Analyses of GPF and its cDNA revealed GPF to be a gamma-carboxyglutamic acid-containing protein encoded by a growth arrest-specific gene, gas6, which related to protein S. GPF specifically potentiated cell proliferation mediated by Ca(2+)-mobilizing receptors. The presence of a specific binding site suggests that the effect of GPF is mediated by a receptor. Thus, GPF may be a new type of extracellular factor regulating VSMC proliferation.
Nakano
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Higashino
K
K
Kikuchi
N
N
Kishino
J
J
Nomura
K
K
Fujita
H
H
Ohara
O
O
Arita
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013917:Thrombin / Q000494:pharmacology; D014462:Ultrafiltration; D000099255:Growth Arrest-Specific Protein 6
D002118:Calcium; D017077:Culture Media, Conditioned; D004247:DNA; D004815:Epidermal Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D013917:Thrombin; D000099255:Growth Arrest-Specific Protein 6