VASCULAR SMOOTH-MUSCLE CELL-DERIVED, GLA-CONTAINING GROWTH-POTENTIATING FACTOR FOR CA2-MOBILIZING GROWTH-FACTORS()

Proliferation of vascular smooth muscle cells (VSMC) is triggered by t wo types of growth factors. One activates tyrosine kinase-type recepto rs and the other activates G-protein-coupled receptors. We found that a conditioned medium of rat VSMC contained a growth-potentiating activ ity for the latter type of growth factor, and we purified a 70-kDa gro wth-potentiating factor (GPF) from the conditioned medium. Analyses of GPF and its cDNA revealed GPF to be a gamma-carboxyglutamic acid-cont aining protein encoded by a growth arrest-specific gene, gas6, which r elated to protein S. GPF specifically potentiated cell proliferation m ediated by Ca2+-mobilizing receptors. The presence of a specific bindi ng site suggests that the effect of GPF is mediated by a receptor. Thu s, GPF may be a new type of extracellular factor regulating VSMC proli feration.