CONTROL OF THE TRANSLATIONAL REGULATORS PHAS-I AND PHAS-II BY INSULINAND AMP IN 3T3-L1 ADIPOCYTES

The eukaryotic initiation factor 4E (eIF-4E)-binding proteins PHAS-I a nd PHAS-II were found to have overlapping but different patterns of ex pression in tissues, Both PHAS proteins were expressed in 3T3-L1 adipo cytes, in which insulin stimulated their phosphorylation, promoted dis sociation of PHAS eIF-4E complexes, and decreased the ability of both to bind exogenous eIF-4E. The effects of insulin were attenuated by ra pamycin and wortmannin, two agents that block activation of p70(S6K). Unlike PHAS-I, PHAS-II was readily phosphorylated by cAMP-dependent pr otein kinase in vitro; however, the effects of insulin on both PHAS pr oteins were attenuated by agents that increase intracellular cAMP, by cAMP derivatives, and by phosphodiesterase inhibitors. These agents al so markedly inhibited the activation of p70(S6K). In summary, our resu lts indicate that PHAS-I and -II are controlled by the mammalian targe t of rapamycin and p70(S6K) Signaling pathway and that in 3T3-L1 adipo cytes this pathway is inhibited by increased cAMP.