Okadaic acid activates atypical protein kinase C (zeta/lambda) in rat and 3T3/L1 adipocytes - An apparent requirement for activation of GLUT4 translocation and glucose transport
Ml. Standaert et al., Okadaic acid activates atypical protein kinase C (zeta/lambda) in rat and 3T3/L1 adipocytes - An apparent requirement for activation of GLUT4 translocation and glucose transport, J BIOL CHEM, 274(20), 1999, pp. 14074-14078
Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, is known to pr
ovoke insulin-like effects on GLUT4 translocation and glucose transport, bu
t the underlying mechanism is obscure. Presently, we found in both rat adip
ocytes and 3T3/L1 adipocytes that okadaic acid provoked partial insulin-lik
e increases in glucose transport, which were inhibited by phosphatidylinosi
tol (PI) 3-kinase inhibitors, wortmannin and LY294002, and inhibitors of at
ypical protein kinase C (PKC) isoforms, zeta and lambda. Moreover, in both
cell types, okadaic acid provoked increases in the activity of immunoprecip
itable PRC-zeta/lambda by a PI 3-kinase-dependent mechanism. In keeping wit
h apparent PI 3-kinase dependence of stimulatory effects of okadaic acid on
glucose transport and PKC-zeta/lambda activity, okadaic acid provoked insu
lin-like increases in membrane PI 3-kinase activity in rat adipocytes; the
mechanism for PI 3-kinase activation was uncertain, however, because it was
not apparent in phosphotyrosine immunoprecipitates. Of further note, okada
ic acid provoked partial insulin-like increases in the translocation of hem
agglutinin antigen-tagged GLUT4 to the plasma membrane in transiently trans
fected rat adipocytes, and these stimulatory effects on hemagglutinin antig
en-tagged GLUT4 translocation were inhibited by eo-expression of kinase;ina
ctive forms of PRC-zeta and PKC-lambda. but not by a double mutant (T308A,
5473A), activation-resistant form of protein kinase B, Our findings suggest
that, as with insulin, PI 3-kinase-dependent atypical PKCs, zeta and lambd
a, are required for okadaic acid-induced increases in GLUT4 translocation a
nd glucose transport in rat adipocytes and 3T3/L1 adipocytes.