Protein kinase C-zeta as a downstream effector of phosphatidylinositol 3-kinase during insulin stimulation in rat adipocytes - Potential role in glucose transport
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Standaert, ML
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机构:JA HALEY VET HOSP,RES SERV VAR 151,TAMPA,FL 33612
Standaert, ML
Galloway, L
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机构:JA HALEY VET HOSP,RES SERV VAR 151,TAMPA,FL 33612
Galloway, L
Karnam, P
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机构:JA HALEY VET HOSP,RES SERV VAR 151,TAMPA,FL 33612
Karnam, P
Bandyopadhyay, G
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机构:JA HALEY VET HOSP,RES SERV VAR 151,TAMPA,FL 33612
Bandyopadhyay, G
Moscat, J
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机构:JA HALEY VET HOSP,RES SERV VAR 151,TAMPA,FL 33612
Moscat, J
Farese, RV
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机构:JA HALEY VET HOSP,RES SERV VAR 151,TAMPA,FL 33612
Farese, RV
机构:
[1] JA HALEY VET HOSP,RES SERV VAR 151,TAMPA,FL 33612
[2] UNIV S FLORIDA,COLL MED,DEPT INTERNAL MED,TAMPA,FL 33612
[3] UNIV S FLORIDA,COLL MED,DEPT BIOCHEM MOL BIOL,TAMPA,FL 33612
[4] UNIV AUTONOMA MADRID,CTR BIO MOL SERVERO OCHOA,MADRID 280049,SPAIN
Insulin provoked rapid increases in enzyme activity of immunoprecipitable protein kinase C-zeta (PKC-zeta) in rat adipocytes. Concomitantly, insulin provoked increases in P-32 labeling of PKC-zeta both in intact adipocytes and during in vitro assay of immunoprecipitated PKC-zeta; the latter probably reflected autophosphorylation, as it was inhibited by the PKC-zeta pseudosubstrate. Insulin-induced activation of immunoprecipitable PKC-zeta was inhibited by LY294002 and wortmannin; this suggested dependence upon phosphatidylinositol (PI) 3-kinase. Accordingly, activation of PI 3-kinase by a pYXXM-containing peptide in vitro resulted in a wortmannin-inhibitable increase in immunoprecipitable PKC-zeta enzyme activity, Also, PI-3,4-(PO4)(2), PI-3,4,5-(PO4)(3), and PI-4,5-(PO4)(2) directly stimulated enzyme activity and autophosphoralytion in control PKC-zeta immunoprecipitates to levels observed in insulin-treated PKC-zeta immunoprecipitates. In studies of glucose transport, inhibition of immunoprecipitated PKC-zeta enzyme activity in vitro by both the PKC-zeta pseudosubstrate and RO 31-8220 correlated well with inhibition of insulin stimulated glucose transport in intact adipocytes. Also, in adipocytes transiently expressing hemagglutinin antigen-tagged GLUT4, co-transfection of wild-type or constitutive PKC-zeta stimulated hemagglutinin antigen-GLUT4 translocation, whereas dominant-negative PKC-zeta partially inhibited it. Our findings suggest that insulin activates PKC-zeta through PI 3-kinase, and PKC-zeta may act as a downstream effector of PI 3-kinase and contribute to the activation of GLUT4 translocation.