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Elongation Factor-2 Phosphorylation and the Regulation of Protein Synthesis by Calcium

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Book cover Signaling Pathways for Translation

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 27))

Abstract

Eukaryotic protein synthesis is a highly regulated process with many of the key proteins being controlled by phosphorylation (for reviews, see Rhoads 1993; Redpath and Proud 1994; Jefferies and Thomas 1996; Merrick and Hershey 1996; Sonenberg and Gingras 1998). Several initiation factors, as well as ribosomal proteins and aminoacyl-tRNA synthetases, are phosphoproteins. While in some cases the physiological role of phosphorylation of these factors is well characterized, in others it remains less clear. In the latter category is elongation factor-2 (eEF2), which catalyzes the translocation of peptidyl-tRNA from the A-site to the P-site on the ribosome. eEF2 is phosphorylated by a highly conserved and specific Ca2+/calmodulin-dependent kinase, termed EF2 kinase (also known as CaM kinase III) at Thr56 and Thr58 (Palfrey and Nairn 1995; Nairn and Palfrey 1996). In vitro, Thr56 is more rapidly phosphorylated by EF2 kinase, and this is sufficient to result in inhibition of protein synthesis. Dephosphorylation of eEF2 by the protein phosphatase 2A (PP2A) results in reactivation of protein synthesis. By implication, similar events in vivo should regulate the rate of elongation and therefore the overall efficiency of protein svnthesis.

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York, 10021, USA

    Angus C. Nairn, Atsuko Horiuchi, Ken-Ichi Mitsui & Yoshio Shimizu

  2. Okayama University Medical School, Okayama, Japan

    Masayuki Matsushita

  3. Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois, 60637, USA

    H. Clive Palfrey

  4. Department of Pathology, University of California, Irvine, California, 92697, USA

    Kent Nastiuk

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  1. Angus C. Nairn
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  1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA

    Robert E. Rhoads

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Nairn, A.C. et al. (2001). Elongation Factor-2 Phosphorylation and the Regulation of Protein Synthesis by Calcium. In: Rhoads, R.E. (eds) Signaling Pathways for Translation. Progress in Molecular and Subcellular Biology, vol 27. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-09889-9_4

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