Signaling Pathways for Translation: Insulin and Nutrients

The articles in the present volume are by major contributors to our under­ standing of signaling pathways affecting protein synthesis. They focus pri­ marily on two extracellular anabolic signals, although others are included as well. Insulin is one of the best-studied extracellular regulators of protein syn­ thesis. Several of the known pathways for regulation of protein synthesis were elucidated using insulin-dependent systems. Regulation of protein synthesis by amino acids, by contrast, is an emerging field that has recently received a great deal of attention. The dual role of amino acids as substrates for protein syn­ thesis and regulators of the overall process has only recently been recognized. Since amino acids serve as precursors for proteins, one might expect that with­ holding an essential amino acid would inhibit the elongation phase. Surpris­ ingly, research has shown that it is the initiation phase of protein synthesis that is restricted during amino acid starvation. Understanding the mechanisms by which the biosynthesis of proteins is reg­ ulated is important for several reasons. Protein synthesis consumes a major portion of the cellular ATP that is generated. Therefore, small changes in protein synthesis can have great consequences for cellular energy metabolism. Translation is also a major site for control of gene expression, since messenger RNAs differ widely in translational efficiency, and changes to the protein syn­ thesis machinery can differentially affect recruitment of individual mRNAs.