// +author:j akanuma +author:akanuma var _ajax_res = { hits: 1, first: 0, results: [ {userid:"junji_yodoi", "articletype":"article","pages":"2729-2734","author":"R Yamamoto-Honda, K Tobe, Y Kaburagi, K Ueki, S Asai, M Yachi, M Shirouzu, J Yodoi, Y Akanuma, S Yokoyama","year":"1995","title":"Upstream mechanisms of glycogen synthase activation by insulin and insulin-like growth factor-I. Glycogen synthase activation is antagonized by wortmannin or LY294002 but not by rapamycin or by inhibiting p21ras.","month":"Feb","journal":"J Biol Chem","publisher":"","volume":"270","number":"6","note":"","tags":"Amino Acid Sequence,Androstadienes,Animals,Chromones,Enzyme Activation,Glycogen Synthase,Insulin,Insulin-Like Growth Factor I,Molecular Sequence Data,Morpholines,Oncogene Protein p21(ras),PC12 Cells,Polyenes,Protein-Serine-Threonine Kinases,Rats,Ribosomal Protein S6 Kinases,Sirolimus","booktitle":"","editor":"","abstract":"This study was undertaken to define intracellular signaling pathways upstream to glycogen synthase activation. First, we examined the role of the two pathways of insulin signaling, Ras-dependent and wortmannin\/LY294002-sensitive, in glycogen synthase activation. Although negative dominant Ras (Ras17N) induction in PC12 cells markedly decreased activities of mitogen-activated protein kinase (MAP) and pp90 S6 kinase in response to insulin or insulin-like growth factor I (IGF-I), activation of glycogen synthase by these agents was unaffected by negative dominant Ras induction. In contrast, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), inhibitors of phosphatidylinositol 3-kinase, antagonized glycogen synthase activation in response to insulin or IGF-I. Next, we examined the contribution of pp70 S6 kinase, one of the wortmannin\/LY294002-sensitive signaling molecules on glycogen synthase activation. Immunosuppressant rapamycin completely blocked activation of pp70 S6 kinase by insulin or IGF-I, but rapamycin alone or in combination with induction of negative dominant Ras failed to antagonize glycogen synthase activation by these hormones. These data suggest that 1) activation of Ras-MAP kinase is not necessary for stimulation of glycogen synthase and 2) activation of wortmannin\/LY294002-sensitive pathway, independent of pp70 S6 kinase, plays a key role in glycogen synthase regulation in PC12 cells.","address":"","school":"","issn":"0021-9258","doi":"","isi":"","pubmed":"7852343","key":"Yamamoto-Honda1995","howpublished":"","urllink":"","refid":302} ] } ; ajaxResultsLoaded(_ajax_res);