Thrombin is the major serum factor stimulating phosphoinositide turnover, but not DNA synthesis in human neuroblastoma SH-EP cells.
Fetal calf serum stimulates both phosphoinositide turnover and DNA synthesis in SH-EP cells. The phosphoinositide turnover-stimulating activity of serum is largely (70%) reduced in the presence of hirudin, a blocker of thrombin activity. Yet, hirudin does not alter the ability of serum to stimulate DNA synthesis. Purified alpha-thrombin is a potent (EC50, 35 pM) stimulator of phosphoinositide turnover in SH-EP cells, but induces DNA synthesis only at much higher concentrations (10 nM-1 microM). Thus, serum thrombin accounts for most of the ability of serum to stimulate phosphoinositide hydrolysis, but not for the effect of serum on cell division, since the concentration of thrombin in serum is not sufficient to induce DNA synthesis. These data suggest that hydrolysis of inositol lipids may not be the main signalling event mediating the mitogenic effects of alpha-thrombin.
Ogino
Y
Y
Laboratory of Theoretical and Physical Biology, NICHD, National Institutes of Health, Bethesda, MD 20892.
Costa
T
T
D001769:Blood; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D009447:Neuroblastoma / Q000737:chemistry* / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D006629:Hirudins; D010716:Phosphatidylinositols; D013917:Thrombin