Dependence of Insulin-Stimulated Glucose Transporter 4 Translocation on 3-Phosphoinositide-Dependent Protein Kinase-1 and Its Target Threonine-410 in the Activation Loop of Protein Kinase C-ζ
| Autor: | Michael J. Quon, L. M. Karnitz, Robert V. Farese, Mary L. Standaert, Gautam Bandyopadhyay, Li-Na Cong, Mini P. Sajan |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Threonine
Monosaccharide Transport Proteins medicine.medical_treatment Muscle Proteins Protein Serine-Threonine Kinases Mitogen-activated protein kinase kinase Transfection MAP2K7 3-Phosphoinositide-Dependent Protein Kinases Epitopes Endocrinology Adipocytes medicine Animals Insulin ASK1 Phosphorylation Protein kinase A Molecular Biology Protein Kinase C Protein kinase C Glucose Transporter Type 4 biology Glucose transporter Biological Transport General Medicine Molecular biology Recombinant Proteins Rats Enzyme Activation Isoenzymes Hemagglutinins Gene Expression Regulation Protein Kinase C-theta Mutation biology.protein GLUT4 |
| Zdroj: | Molecular Endocrinology. 13:1766-1772 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Previous studies have suggested that 1) atypical protein kinase C (PKC) isoforms are required for insulin stimulation of glucose transport, and 2) 3-phosphoinositide-dependent protein kinase-1 (PDK-1) is required for activation of atypical PKCs. Presently, we evaluated the role of PDK-1, both in the activation of PKC-zeta, and the translocation of epitope-tagged glucose transporter 4 (GLUT4) to the plasma membrane, during insulin action in transiently transfected rat adipocytes. Overexpression of wild-type PDK-1 provoked increases in the activity of cotransfected hemagglutinin (HA)-tagged PKC-zeta and concomitantly enhanced HA-tagged GLUT4 translocation. Expression of both kinase-inactive PDK-1 and an activation-resistant form of PKC-zeta that is mutated at Thr-410, the immediate target of PDK-1 in the activation loop of PKC-zeta, inhibited insulin-induced increases in both HA-PKC-zeta activity and HA-GLUT4 translocation to the same extent as kinase-inactive PKC-zeta. Moreover, the inhibitory effects of kinase-inactive PDK-1 were fully reversed by cotransfection of wild-type PDK-1 and partly reversed by wild-type PKC-zeta, but not by wild-type PKB. In contrast to the T410A PKC-zeta mutant, an analogous double mutant of PKB (T308A/S473A) that is resistant to PDK-1 activation had only a small effect on insulin-stimulated HA-GLUT4 translocation and did not inhibit HA-GLUT4 translocation induced by overexpression of wild-type PDK-1. Our findings suggest that both PDK-1 and its downstream target, Thr-410 in the activation loop of PKC-zeta, are required for insulin-stimulated glucose transport. |
| Databáze: | OpenAIRE |
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