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

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.