Differential protein phosphorylation in 3T3-L1 adipocytes in response to insulin versus platelet-derived growth factor - No evidence for a phosphatidylinositide 3-kinase-independent pathway in insulin signaling
- Author(s)
- Hill, MM; Connolly, LM; Simpson, RJ; James, DE;
- Details
- Publication Year 2000-08-11,Volume 275,Issue #32,Page 24313-24320
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- Insulin regulates glucose metabolism in adipocytes via a phosphatidylinositide 3-kinase (PI3K)-dependent pathway that appears to involve protein phosphorylation, However, the generation of phosphoinositides is not sufficient for insulin action, and it has been suggested that insulin regulation of glucose metabolism may involve both PI3K-dependent and -independent pathways, the latter being insulin specific. To test this hypothesis, we have designed a phosphoprotein screen to study insulin-specific phosphoproteins that may be either downstream or in parallel to PI3K, Nineteen insulin-regulated phosphospots were detected in the cytosol and high speed pellet fractions, only six of which were significantly regulated by platelet-derived growth factor. importantly, almost all (92%) of the insulin-specific phosphoproteins identified using this approach were sensitive to the PI3K inhibitor wortmannin, Thus, we obtained no evidence for an insulin-specific, PI3K-independent signaling pathway. A large proportion (62%) of the insulin-specific phosphoproteins mere enriched in the same high speed pellet fraction to which PI3K was recruited in response to insulin. Thus, our data suggest that insulin specifically stimulates the phosphorylation of a novel subset of downstream targets and this may in part be because of the unique localization of PI3K in response to insulin in adipocytes.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- ELONGATION FACTOR-II; ATP-CITRATE LYASE; RAT ADIPOSE-CELLS; PHOSPHOINOSITIDE 3-KINASE; GLUT4 TRANSLOCATION; GLUCOSE-TRANSPORT; GEL-ELECTROPHORESIS; POLYACRYLAMIDE GELS; SER/THR KINASE; ACTIVATION
- Publisher's Version
- https://doi.org/10.1074/jbc.M001823200
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- Refer to copyright notice on published article.
Creation Date: 2000-08-11 12:00:00