G. Condorelli et al., Protein kinase C (PKC)-alpha activation inhibits PKC-zeta and mediates theaction of PED/PEA-15 on glucose transport in the L6 skeletal muscle cells, DIABETES, 50(6), 2001, pp. 1244-1252
Overexpression of the PED/PEA-15 protein in muscle and adipose cells increa
ses glucose transport and impairs further insulin induction. Like glucose t
ransport, protein kinase C (PKC)-alpha: and -beta are also constitutively a
ctivated and are not further stimulatable by insulin in L6 skeletal muscle
cells overexpressing PED (L6(PED)). PKC-xi features no basal change but com
pletely loses insulin sensitivity in L6(PED). In these cells, blockage of P
KC-alpha and -beta additively returns 2-deoxy-D-glucose (2-DG) uptake to th
e 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 effe
cts 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 wit
h no effect on insulin receptor or insulin receptor substrate phosphorylati
on. 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 inhi
biting PKC-xi stimulation. Expression of the dominant-negative K-281-->W PK
C-xi mutant simultaneously inhibits insulin activation of PKC-xi and 2-DG u
ptake in the L6(WT) cells. Me conclude that; activation of classic PKCs, ma
inly PRC-alpha, inhibits PKC-xi and may mediate the action of PED on glucos
e uptake in L6 skeletal muscle cells.