Lin T A, Lawrence J C
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Biol Chem. 1996 Nov 22;271(47):30199-204. doi: 10.1074/jbc.271.47.30199.
The eukaryotic initiation factor 4E (eIF-4E)-binding proteins PHAS-I and PHAS-II were found to have overlapping but different patterns of expression in tissues. Both PHAS proteins were expressed in 3T3-L1 adipocytes, in which insulin stimulated their phosphorylation, promoted dissociation of PHAS.eIF-4E complexes, and decreased the ability of both to bind exogenous eIF-4E. The effects of insulin were attenuated by rapamycin and wortmannin, two agents that block activation of p70(S6K). Unlike PHAS-I, PHAS-II was readily phosphorylated by cAMP-dependent protein kinase in vitro; however, the effects of insulin on both PHAS proteins were attenuated by agents that increase intracellular cAMP, by cAMP derivatives, and by phosphodiesterase inhibitors. These agents also markedly inhibited the activation of p70(S6K). In summary, our results indicate that PHAS-I and -II are controlled by the mammalian target of rapamycin and p70(S6K) signaling pathway and that in 3T3-L1 adipocytes this pathway is inhibited by increased cAMP.
真核生物起始因子4E（eIF - 4E）结合蛋白PHAS - I和PHAS - II在组织中呈现出重叠但不同的表达模式。两种PHAS蛋白均在3T3 - L1脂肪细胞中表达，胰岛素可刺激其磷酸化，促进PHAS·eIF - 4E复合物解离，并降低两者结合外源性eIF - 4E的能力。胰岛素的作用被雷帕霉素和渥曼青霉素减弱，这两种药物可阻断p70（S6K）的激活。与PHAS - I不同，PHAS - II在体外可被环磷酸腺苷（cAMP）依赖性蛋白激酶轻易磷酸化；然而，胰岛素对两种PHAS蛋白的作用被增加细胞内cAMP的药物、cAMP衍生物以及磷酸二酯酶抑制剂减弱。这些药物也显著抑制p70（S6K）的激活。总之，我们的结果表明，PHAS - I和 - II受雷帕霉素的哺乳动物靶点和p70（S6K）信号通路调控，并且在3T3 - L1脂肪细胞中，该通路被增加的cAMP抑制。
