Atypical protein kinase (PK)C isoforms, ζ and λ, have been reported to be activated by insulin via phosphoinositide 3-kinase, and have been suggested to be required for insulin-stimulated glucose transport. Here, we have examined the effects of transiently expressed wild-type (WT), constitutively active (Constit) and kinase-inactive (KI) forms of atypical PKCs, ζ and λ, on haemagglutinin antigen (HAA)-tagged glucose transporter 4 (GLUT4) translocation in rat adipocytes, and compared these effects with each other and with those of comparable forms of conventional (α, β) and novel (δ, ε) PKCs, which have also been proposed to be required for insulin-stimulated glucose transport. KI-PKC-ζ evoked consistent, sizeable (overall mean of 65%) inhibitory effects on insulin-stimulated, but not basal or guanosine-5´-[γ-thio]triphosphate-stimulated, HAA-GLUT4 translocation; moreover, inhibitory effects of KI-PKC-ζ were largely reversed by co-transfection of WT-PKC-ζ. Like KI-PKC-ζ, KI-PKC-λ inhibited insulin-stimulated HAA-GLUT4 translocation by approx. 40–60%, and the combination of KI-PKC-ζ and KI-PKC-λ caused nearly complete (85%) inhibition. Of particular interest is the fact that inhibitory effects of KI forms of PKC-ζ and PKC-λ were largely reversed by the opposite WT forms, i.e. PKC-λ and PKC-ζ respectively. In contrast with KI forms of atypical PKCs, KI forms of PKC-α, PKC-β2, PKC-δ and PKC-ε had little or no effect on insulin-stimulated HAA-GLUT4 translocation. Concerning the question of sufficiency, overexpression of WT-PKC-ζ enhanced insulin effects on HAA-GLUT4 translocation, whereas WT forms of PKC-α, PKC-β2, PKC-δ and PKC-ε did not affect GLUT4 translocation; furthermore, Constit PKC-ζ evoked increases in HAA-GLUT4 translocation approaching those of insulin, but Constit forms of PKC-α and PKC-β2 were without effect. Our findings suggest that, among PKCs, the atypical PKCs, ζ and λ, appear to be specifically, but interchangeably, required for insulin effects on HAA-GLUT4 translocation.
Effects of transiently expressed atypical (ζ, λ), conventional (α, β) and novel (δ, ɛ) protein kinase C isoforms on insulin-stimulated translocation of epitope-tagged GLUT4 glucose transporters in rat adipocytes: specific interchangeable effects of protein kinases C-ζ and C-λ
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Gautam BANDYOPADHYAY, Mary L. STANDAERT, Ushio KIKKAWA, Yoshitaka ONO, Jorge MOSCAT, Robert V. FARESE; Effects of transiently expressed atypical (ζ, λ), conventional (α, β) and novel (δ, ɛ) protein kinase C isoforms on insulin-stimulated translocation of epitope-tagged GLUT4 glucose transporters in rat adipocytes: specific interchangeable effects of protein kinases C-ζ and C-λ. Biochem J 1 February 1999; 337 (3): 461–470. doi: https://doi.org/10.1042/bj3370461
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