Abstract
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.
Highlights
Proliferation of vascular smooth muscle cells (VSMC) is triggered by two types of growth factors
Assay for growth-potentiating factor (GPF) Activity-Confluent rat VSMCs in 24-well tissue culture plates were cultured for 48 h in DMEM containing 0.1% BSA
One hypothesis for the mechanism of mitogenesis induced by Ca 2 + -mobilizing receptors is that the mitogenesis is due to secondarily produced tyrosine kinase-activating growth factors
Summary
Vascular Smooth Muscle Cell-derived, Gla-containing Growth-potentiating Factor for Ca2 +-mobilizing Growth Factors*. From the Shionogi Research Laboratories, Shionogi & Co., Ltd., 5-12-4 Sagisu, Fukushima-ku, Osaka 553, Japan by several factors such as thrombin, angiotensin-11, or lysophosphatidic acid, which are candidates for intimal thickening of the vascular wall [5,6,7]. It is not clear why these two distinct signaling mechanisms lead to the same output, i.e. mitogenesis. Proliferation of vascular smooth muscle cells (VSMC) is triggered by two types of growth factors. §Present address: Laboratory of DNA Technology, Kazusa DNA Research Inst., 1532-3 Yana-Uchino, Kisarazu-shi, Chiba 292, Japan
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