10 Regulation of Protein Synthesis by Calcium

Abstract

Eukaryotic protein synthesis is highly regulated by a variety of acute and chronic processes. Paramount among these processes is the reversible phosphorylation of protein synthetic components. Many of the factors involved in translation are phosphoproteins, and a certain amount is known about the kinases and phosphatases responsible for the phosphorylation and dephosphorylation of these factors. Considerably less is known about the overall physiological role of phosphorylation of translational components. In particular, two aspects remain to be fully understood, namely, the general involvement of Ca⁺⁺ in the regulation of protein synthesis and specifically, the role of Ca⁺⁺-dependent phosphorylation of elongation factor-2 (eEF2). This chapter reviews these two topics. For more detailed reviews of the mechanistic details of protein synthesis and the role of protein phosphorylation in protein synthesis, see Merrick and Hershey, Trachsel, Clemens, and Hinnebusch (all this volume).

REGULATION OF PROTEIN SYNTHESIS ELONGATION BY CA⁺⁺
Identification of eEF2 Phosphorylation
It has generally been assumed that initiation is the key regulatory step in protein synthesis and that changes in elongation rate could only affect global rates of translation without any type of specificity. However, increasing evidence suggests that elongation rates are subject to several forms of control and that this may result in selective effects on the translation of certain messenger RNAs (for further discussion, see below). An important factor in this renewed interest in the regulation of elongation is the discovery that both of the factors involved in polypeptide elongation, namely, eEF1 and eEF2 (see Merrick and Hershey, this volume),...