title: Protein kinase C (PKC)-alpha activation inhibits PKC-zeta and mediates the action of PED/PEA-15 on glucose transport in the L6 skeletal muscle cells.
abstract: Overexpression of the PED/PEA-15 protein in muscle and adipose cells increases glucose transport and impairs further insulin induction. Like glucose transport, protein kinase C (PKC)-alpha and -beta are also constitutively activated and are not further stimulatable by insulin in L6 skeletal muscle cells overexpressing PED (L6(PED)). PKC-zeta features no basal change but completely loses insulin sensitivity in L6(PED). In these cells, blockage of PKC-alpha and -beta additively returns 2-deoxy-D-glucose (2-DG) uptake to the levels of cells expressing only endogenous PED (L6(WT)). Blockage of PKC-alpha and -beta also restores insulin activation of PKC-zeta in L6(PED) cells, with that of PKC-alpha sixfold more effective than PKC-beta. Similar effects on 2-DG uptake and PKC-zeta were also achieved by 50-fold overexpression of PKC-zeta in L6(PED). In L6(WT), fivefold overexpression of PKC-alpha or -beta increases basal 2-DG uptake and impairs further insulin induction with no effect on insulin receptor or insulin receptor substrate phosphorylation. In these cells, overexpression of PKC-alpha blocks insulin induction of PKC-zeta activity. PKC-beta is 10-fold less effective than PKC-alpha in inhibiting PKC-zeta stimulation. Expression of the dominant-negative K(281)-->W PKC-zeta mutant simultaneously inhibits insulin activation of PKC-zeta and 2-DG uptake in the L6(WT) cells. We conclude that activation of classic PKCs, mainly PKC-alpha, inhibits PKC-zeta and may mediate the action of PED on glucose uptake in L6 skeletal muscle cells.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Federico II University of Naples, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Condorelli
authors.forename: G
authors.initials: G
authors.lastname: Vigliotta
authors.forename: A
authors.initials: A
authors.lastname: Trencia
authors.forename: M A
authors.initials: MA
authors.lastname: Maitan
authors.forename: M
authors.initials: M
authors.lastname: Caruso
authors.forename: C
authors.initials: C
authors.lastname: Miele
authors.forename: F
authors.initials: F
authors.lastname: Oriente
authors.forename: S
authors.initials: S
authors.lastname: Santopietro
authors.forename: P
authors.initials: P
authors.lastname: Formisano
authors.forename: F
authors.initials: F
authors.lastname: Beguinot
mesh_terms: D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D016296:Mutagenesis; D010750:Phosphoproteins / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D014162:Transfection; D000099221:Protein Kinase C zeta
chemical_list: D051017:Apoptosis Regulatory Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D009004:Monosaccharide Transport Proteins; D010750:Phosphoproteins; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D000099221:Protein Kinase C zeta; C092039:PEA15 protein, human; C032907:Q surface antigens