| Co-Investigator(Kenkyū-buntansha) |
NISHINA Hiroshi University of Tokyo, Graduate School of Pharmaceutical Science, Assistant, 大学院・薬学系研究科, 助手 (60212122)
HOSHINO Shin'ichi University of Tokyo, Graduate School of Pharmaceutical Science, Assistant, 大学院・薬学系研究科, 助手 (40219168)
KATADA Toshiaki University of Tokyo, Graduate School of Pharmaceutical Science, Professor, 大学院・薬学系研究科, 教授 (10088859)
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| Research Abstract |
Two types of phosphoinositide 3-kinase (PI 3-kinase), in terms of the mechanism of activation, had been recognized. One is stimulated by a tyrosine-phosphorylated peptide (PY). The other is activated by the betagamma subunits of GTP-binding proteins (GBgamma). In the present study, we found the activity which is stimulated by both PY and GBgamma in a synergistic manner. The activity was identified to be the beta-subtype of PI 3-kinase. In rat adipocyted, cell production of phsphatidylinositol-3,4,5-trisphosphate, a product of PI 3-kinase, increased synergistically by insulin (tyrosine kinase-activating) and adenosine (G-protein-activating). Similar results were observed in the CHO cells artificially transfected with the insulin and fMLP receptors. Insulin actions on these cells (glucose uptake, memrane ruffling) were effectively potentiated by simultaneous stimulation of the GTP-binding proteins. This effect of GTP-binding proteins was accompanied by the potentiation of insulin-induced activation of protein kinase B,a putative downstream target of PI 3-kinases. The results indicated a novel role of GTP-binding proteins, a permissive regulation of the insulin receptor-derived signal.
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