RETRACTED: Protein kinase C (PKC)-α activation inhibits PKC-ζ and mediates the action of PED/PEA-15 on glucose transport in the L6 skeletal muscle cells (Publication with Expression of Concern. See vol. 67, 2018) (Retracted article. See vol. 68, pg. 464, 2019)

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-xi 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-xi in L6(PED) cells, with that of PKC-alpha sixfold more effective than PKC-beta. Similar effects on 2-DG uptake and PKC-xi were also achieved by 50-fold overexpression of PKC-alpha in L6(PED). In L6(WT) fivefoId 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-xi activity. PKC-beta is 10-fold less effective than PKC-alpha in inhibiting PKC-xi stimulation. Expression of the dominant-negative K-281-->W PKC-xi mutant simultaneously inhibits insulin activation of PKC-xi and 2-DG uptake in the L6(WT) cells. Me conclude that; activation of classic PKCs, mainly PRC-alpha, inhibits PKC-xi and may mediate the action of PED on glucose uptake in L6 skeletal muscle cells.