Regulation of eukaryotic protein synthesis by protein kinases that phosphorylate initiation factor eIF-2: Further evidence for a common mechanism of inhibition of protein synthesis

This paper reviews the evidence that protein synthesis in rabbit reticulocytes is regulated by the reversible phosphorylation of the initiation factor eIF-2 by protein kinases under the control of the cytoplasmic haemin concentration on the one hand, and double-stranded RNA on the other. A molecular mechanism is proposed to account for the observation that inhibition of protein synthesis occurs when considerably less than half the eIF-2 present has been phosphorylated. The question of whether phosphorylation regulates protein synthesis in other types of cell is discussed.

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Regulation of eukaryotic protein synthesis by protein kinases that phosphorylate initiation factor eIF-2

Molecular Biology Reports ◽

10.1007/bf00986962 ◽

1994 ◽

Vol 19 (3) ◽

pp. 201-210 ◽

Cited By ~ 29

Author(s):

Michael J. Clemens

Keyword(s):

Protein Synthesis ◽

Protein Kinases ◽

Initiation Factor ◽

Eukaryotic Protein

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Roles of Eukaryotic Initiation Factor 2 Ancillary Factors in the Regulation of Eukaryotic Protein Synthesis Initiation

Current Topics in Cellular Regulation ◽

10.1016/b978-0-12-152821-8.50005-0 ◽

1982 ◽

pp. 1-33 ◽

Cited By ~ 10

Author(s):

NABA K. GUPTA

Keyword(s):

Protein Synthesis ◽

Initiation Factor ◽

Eukaryotic Initiation Factor ◽

Eukaryotic Protein ◽

Eukaryotic Initiation Factor 2 ◽

Initiation Factor 2 ◽

Protein Synthesis Initiation

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The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bɛ at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase

Biochemical Journal ◽

10.1042/bj3550609 ◽

2001 ◽

Vol 355 (3) ◽

pp. 609-615 ◽

Cited By ~ 184

Author(s):

Yvonne L. WOODS ◽

Philip COHEN ◽

Walter BECKER ◽

Ross JAKES ◽

Michel GOEDERT ◽

...

Keyword(s):

Protein Synthesis ◽

Protein Kinases ◽

Glycogen Synthase ◽

Glycogen Synthase Kinase ◽

Initiation Factor ◽

Glycogen Synthase Kinase 3 ◽

General Role ◽

Protein Tau ◽

Microtubule Associated Protein Tau ◽

Protein Synthesis Initiation

The substrate specificity of glycogen synthase kinase 3 (GSK3) is unusual in that efficient phosphorylation only occurs if another phosphoserine or phosphothreonine residue is already present four residues C-terminal to the site of GSK3 phosphorylation. One such substrate is the ε-subunit of rat eukaryotic protein-synthesis initiation factor 2B (eIF2Bε), which is inhibited by the GSK3-catalysed phosphorylation of Ser535. There is evidence that GSK3 is only able to phosphorylate eIF2Bε at Ser535 if Ser539 is already phosphorylated by another protein kinase. However, no protein kinases capable of phosphorylating Ser539 have so far been identified. Here we show that Ser539 of eIF2Bε, which is followed by proline, is phosphorylated specifically by two isoforms of dual-specificity tyrosine phosphorylated and regulated kinase (DYRK2 and DYRK1A), but only weakly or not at all by other ‘proline-directed’ protein kinases tested. We also establish that phosphorylation of Ser539 permits GSK3 to phosphorylate Ser535in vitro and that eIF2Bε is highly phosphorylated at Ser539in vivo. The DYRK isoforms also phosphorylate human microtubule-associated protein tau at Thr212in vitro, a residue that is phosphorylated in foetal tau and hyperphosphorylated in filamentous tau from Alzheimer's-disease brain. Phosphorylation of Thr212 primes tau for phosphorylation by GSK3 at Ser208in vitro, suggesting a more general role for DYRK isoforms in priming phosphorylation of GSK3 substrates.

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