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4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle Shah OJ; Anthony JC; Kimball SR; Jefferson LSAm J Physiol Endocrinol Metab 2000[Oct]; 279 (4): E715-29Maintenance of cellular protein stores in skeletal muscle depends on a tightly regulated synthesis-degradation equilibrium that is conditionally modulated under an extensive range of physiological and pathophysiological circumstances. Recent studies have established the initiation phase of mRNA translation as a pivotal site of regulation for global rates of protein synthesis, as well as a site through which the synthesis of specific proteins is controlled. The protein synthetic pathway is exquisitely sensitive to the availability of hormones and nutrients and employs a comprehensive integrative strategy to interpret the information provided by hormonal and nutritional cues. The translational repressor, eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and the 70-kDa ribosomal protein S6 kinase (S6K1) have emerged as important components of this strategy, and together they coordinate the behavior of both eukaryotic initiation factors and the ribosome. This review discusses the role of 4E-BP1 and S6K1 in translational control and outlines the mechanisms through which hormones and nutrients effect changes in mRNA translation through the influence of these translational effectors.|*Protein Kinases[MESH]|Amino Acids/metabolism[MESH]|Animals[MESH]|Cricetinae[MESH]|Eukaryotic Initiation Factor-4E[MESH]|Glucocorticoids/metabolism[MESH]|Growth Substances/metabolism[MESH]|Hormones/*metabolism[MESH]|Humans[MESH]|Insulin/metabolism[MESH]|Muscle, Skeletal/*metabolism[MESH]|Peptide Initiation Factors/*metabolism[MESH]|Phosphoprotein Phosphatases/metabolism[MESH]|Phosphotransferases (Alcohol Group Acceptor)/metabolism[MESH]|Phosphotransferases/metabolism[MESH]|Protein Biosynthesis/*genetics[MESH]|RNA, Messenger/genetics[MESH]|Rats[MESH]|Ribosomal Protein S6 Kinases/*metabolism[MESH]|Signal Transduction/*genetics[MESH]|Starvation/metabolism[MESH]|TOR Serine-Threonine Kinases[MESH] |
