Regulation of protein synthesis by IGF-I in proximal tubular epithelial cells.
Regulation of protein synthesis by IGF-I in proximal tubular epithelial cells.
复制标题
IGF-I 对近端肾小管上皮细胞中蛋白质合成的调节。
DOI：
10.1152/ajprenal.00109.2002
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Kasinath,BalakuntalamS
中科院分区：
文献类型：
--
作者：
Senthil,Duraisamy;Choudhury,GoutamGhosh;Abboud,HannaE;Sonenberg,Nahum;Kasinath,BalakuntalamS
Protein synthesis is required for renal hypertrophy, and proximal tubular epithelial cells are an important cell type involved in this process. We examined IGF-I regulation of protein synthesis in murine proximal tubular epithelial (MCT) cells. We focused on initial events in protein translation and the signaling events involved. Translation of capped mRNAs is under the control of eukaryotic initiation factor 4E (eIF4E). In the resting cell, eIF4E is normally kept in an inactive state by binding to 4E-BP1, its binding protein. Phosphorylation of 4E-BP1 results in dissociation of the eIF4E-4E-BP1 complex allowing eIF4E to initiate peptide synthesis. IGF-I stimulated protein synthesis, augmented phosphorylation of 4E-BP1 and promoted the dissociation of eIF4E from 4E-BP1. IGF-I stimulated the activities of phosphatidylinositol (PI) 3-kinase, Akt, and ERK1/2-type MAPK in MCT cells. IGF-I-induced phosphorylation of 4E-BP1, dissociation of the 4E-BP1-eIF4E complex, and increase in protein synthesis required activation of both PI 3-kinase and ERK pathways. Furthermore, ERK activation by IGF-I was also PI 3-kinase dependent. Transfection with the Thr37,46→Ala37,46mutant of 4E-BP1 showed that phosphorylation of Thr37,46residues was required for IGF-I induction of protein synthesis in MCT cells. Our observations reveal the importance of initial events in protein translation in IGF-I-induced protein synthesis in MCT cells and identify the regulatory signaling pathways involved.
