Kimball S R, Jefferson L S, Fadden P, Haystead T A, Lawrence J C
Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Am J Physiol. 1996 Feb;270(2 Pt 1):C705-9. doi: 10.1152/ajpcell.1996.270.2.C705.
We have investigated the roles of eukaryotic initiation factor 4E (eIF-4E), the cap-binding protein, and the translational regulator, PHAS-I, in the effects of insulin and alloxan-induced diabetes on protein synthesis in rat skeletal muscle. Diabetes increased the amount of eIF-4E found in the inactive PHAS-I.eIF-4E complex by threefold, explaining in part the inhibitory effect of insulin deficiency on translation initiation. Insulin treatment of diabetic rats caused dissociation of the complex, consistent with the action of the hormone on reversing the inhibitory effect of diabetes on translation initiation. The effects of both insulin and diabetes on PHAS-I binding to eIF-4E appeared to be due to changes in PHAS-I phosphorylation. Neither insulin nor diabetes changed the phosphorylation state of eIF-4E. The results indicate that the effects of both insulin and diabetes on protein synthesis in skeletal muscle involve modulation of the interaction of PHAS-I and eIF-4E.
我们研究了真核生物起始因子4E（eIF-4E，即帽结合蛋白）和翻译调节因子PHAS-I在胰岛素及四氧嘧啶诱导的糖尿病对大鼠骨骼肌蛋白质合成影响中的作用。糖尿病使非活性PHAS-I·eIF-4E复合物中的eIF-4E含量增加了三倍，部分解释了胰岛素缺乏对翻译起始的抑制作用。用胰岛素治疗糖尿病大鼠会导致该复合物解离，这与该激素逆转糖尿病对翻译起始抑制作用的效果一致。胰岛素和糖尿病对PHAS-I与eIF-4E结合的影响似乎是由于PHAS-I磷酸化状态的改变。胰岛素和糖尿病均未改变eIF-4E的磷酸化状态。结果表明，胰岛素和糖尿病对骨骼肌蛋白质合成的影响均涉及对PHAS-I与eIF-4E相互作用的调节。
