Abstract
The serine/threonine phosphatase inhibitor, okadaic acid (OA), exerted several insulin-like effects in rat adipose cells and was, in part, synergistic with insulin. OA stimulated glucose transport activity, altered the electrophoretic mobility of IRS-1, increased the phosphorylation of the MAP-kinases ERK 1 and 2 on tyrosine sites, markedly increased MAP kinase activity and also acted synergistically with insulin in activating these enzymes. However, OA did not increase PI 3-kinase activity or the tyrosine phosphorylation of key upstream proteins in insulin's signaling cascade. Staurosporine virtually completely inhibited the insulin-stimulated glucose transport and MAP kinase activation in spite of a maintained high PI 3-kinase activity. In contrast, the effects of OA alone or in the presence of insulin were less, or not at all, affected. These data suggest that OA exerts an insulin-like effect through a serine/threonine-related pathway which is distinct from, but converges with, that of insulin downstream PI 3-kinase and upon which staurosporine exerts an inhibitory effect.
References
Jul 10, 1992·Cell·G PelicciP G Pelicci
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J J EganC Londos
Feb 15, 1990·Nature·N G AndersonT W Sturgill
Apr 1, 1990·Current Opinion in Cell Biology·S Jaken
Apr 7, 1989·Cell·K R AugerL C Cantley
Jan 1, 1989·Annual Review of Biochemistry·P Cohen
Jan 5, 1989·Nature·T A HaysteadD G Hardie
Nov 15, 1988·The Biochemical Journal·C Bialojan, A Takai
Dec 30, 1988·Biochemical and Biophysical Research Communications·Y Fujita-Yamaguchi, S Kathuria
Apr 6, 1995·Biochemical and Biophysical Research Communications·K KotaniM Kasuga
Feb 3, 1995·The Journal of Biological Chemistry·J I YehM J Birnbaum
Jul 1, 1994·Molecular and Cellular Biology·B CheathamC R Kahn
Aug 15, 1994·The Biochemical Journal·H Nishimura, I A Simpson
Apr 29, 1994·Biochemical Pharmacology·A Shisheva, Y Shechter
Citations
Nov 7, 2009·Cancer Chemotherapy and Pharmacology·Shivaani KummarJames H Doroshow
Jan 17, 2012·The British Journal of Dermatology·G EvangelouL E Rhodes
Oct 12, 2019·Photochemistry and Photobiology·Shubhankar NathTayyaba Hasan
Jul 12, 2003·Blood·De YangJoost J Oppenheim