Knockout of PKCα Enhances Insulin Signaling Through PI3K
- 1 April 2002
- journal article
- Published by The Endocrine Society in Molecular Endocrinology
- Vol. 16 (4) , 847-858
- https://doi.org/10.1210/mend.16.4.0809
Abstract
Insulin stimulates glucose transport and certain other metabolic processes by activating atypical PKC isoforms (lambda, zeta, iota) and protein kinase B (PKB) through increases in D3-polyphosphoinositides derived from the action of PI3K. The role of diacylglycerol-sensitive PKC isoforms is less clear as they have been suggested to be both activated by insulin and yet inhibit insulin signaling to PI3K. Presently, we found that insulin signaling to insulin receptor substrate 1-dependent PI3K, PKB, and PKC lambda, and downstream processes, glucose transport and activation of ERK, were enhanced in skeletal muscles and adipocytes of mice in which the ubiquitous conventional diacylglycerol-sensitive PKC isoform, PKC alpha, was knocked out by homologous recombination. On the other hand, insulin provoked wortmannin-insensitive increases in immunoprecipitable PKC alpha activity in adipocytes and skeletal muscles of wild-type mice and rats. We conclude that 1) PKC alpha is not required for insulin-stimulated glucose transport, and 2) PKC alpha is activated by insulin at least partly independently of PI3K, and largely serves as a physiological feedback inhibitor of insulin signaling to the insulin receptor substrate 1/PI3K/PKB/PKC lambda/zeta/iota complex and dependent metabolic processes.Keywords
This publication has 30 references indexed in Scilit:
- Insulin and PIP3 Activate PKC-ζ by Mechanisms That Are Both Dependent and Independent of Phosphorylation of Activation Loop (T410) and Autophosphorylation (T560) SitesBiochemistry, 2000
- Thiazolidinedione Treatment Enhances Insulin Effects on Protein Kinase C-ζ/λ Activation and Glucose Transport in Adipocytes of Nondiabetic and Goto-Kakizaki Type II Diabetic RatsJournal of Biological Chemistry, 2000
- Restored insulin-sensitivity in IRS-1–deficient mice treated by adenovirus-mediated gene therapyJournal of Clinical Investigation, 2000
- Protein Kinase C-ζ and Phosphoinositide-dependent Protein Kinase-1 Are Required for Insulin-induced Activation of ERK in Rat AdipocytesPublished by Elsevier ,1999
- In Vivo Adenoviral Delivery of Recombinant Human Protein Kinase C-ζ Stimulates Glucose Transport Activity in Rat Skeletal MusclePublished by Elsevier ,1999
- Protein Kinase C-ζ as a Downstream Effector of Phosphatidylinositol 3-Kinase during Insulin Stimulation in Rat AdipocytesPublished by Elsevier ,1997
- Activation of Protein Kinase C (α, β, and ζ) by Insulin in 3T3/L1 CellsJournal of Biological Chemistry, 1997
- Expression of a Constitutively Active Akt Ser/Thr Kinase in 3T3-L1 Adipocytes Stimulates Glucose Uptake and Glucose Transporter 4 TranslocationJournal of Biological Chemistry, 1996
- Threonine 1336 of the human insulin receptor is a major target for phosphorylation by protein kinase CBiochemistry, 1990
- Identification of a phosphorylation site of the rat insulin receptor catalyzed by protein kinase C in an intact cellFEBS Letters, 1989