Regulation of protein synthesis: activation by double-stranded RNA of a protein kinase that phosphorylates eukaryotic initiation factor 2 - PubMed (original) (raw)

Regulation of protein synthesis: activation by double-stranded RNA of a protein kinase that phosphorylates eukaryotic initiation factor 2

D Levin et al. Proc Natl Acad Sci U S A. 1978 Mar.

Abstract

Incubation of reticulocyte lysates or isolated crude ribosomes with low levels of double-stranded RNA (0.1-10 ng/ml) induces the formation of an inhibitor of protein synthesis initiation similar to that observed in heme deficiency. The inhibitor is associated with a cyclic AMP-independent protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) that phosphorylates the small polypeptide (38,000 daltons) of the eukaryotic initiation factor eIF-2. Activation of the inhibitor requires ATP in addition to double-stranded RNA and is accompanied by the phosphorylation of a 67,000-dalton polypeptide of unknown function. The inhibitor remains associated with the ribosomes during high-speed sedimentation. Once formed, the ribosome-associated inhibitor phosphorylates eIF-2 and inhibits protein synthesis in the absence of double-stranded RNA. Inhibition is prevented by exogenous eIF-2. The bound inhibitor can be solubilized by extraction with 0.5 M KCl. The soluble inhibitor preparation retains the ability to phosphorylate the small polypeptide of eIF-2 and to inhibit protein synthesis. Untreated crude ribosomes also contain cyclic AMP-independent protein kinase activities that phosphorylate the middle polypeptide (49,000 daltons) of eIF-2 and several polypeptide subunits of eIF-3 (160,000, 125,000, and 65,000 daltons); these kinase activities are not affected by double-stranded RNA and do not inhibit protein synthesis.

PubMed Disclaimer

Similar articles

• Characterization of double-stranded-RNA-activated kinase that phosphorylates alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha) in reticulocyte lysates.
  Levin DH, Petryshyn R, London IM. Levin DH, et al. Proc Natl Acad Sci U S A. 1980 Feb;77(2):832-6. doi: 10.1073/pnas.77.2.832. Proc Natl Acad Sci U S A. 1980. PMID: 6928683 Free PMC article.
• Regulation of double-stranded RNA-activated eukaryotic initiation factor 2 alpha kinase by type 2 protein phosphatase in reticulocyte lysates.
  Petryshyn R, Levin DH, London IM. Petryshyn R, et al. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6512-6. doi: 10.1073/pnas.79.21.6512. Proc Natl Acad Sci U S A. 1982. PMID: 6292906 Free PMC article.
• Regulation of protein synthesis.
  Ochoa S. Ochoa S. Eur J Cell Biol. 1979 Jun;19(2):95-101. Eur J Cell Biol. 1979. PMID: 223849 Review.
• Regulation of translation.
  Ochoa S. Ochoa S. Arch Biol Med Exp. 1979 Oct;12(3):295-307. Arch Biol Med Exp. 1979. PMID: 233291 Review. No abstract available.

Cited by

• The making of a nucleic acid sensor at the dawn of jawed vertebrate evolution.
  Wu Z, Chu L, Gong Z, Han GZ. Wu Z, et al. Sci Adv. 2024 Aug 9;10(32):eado7464. doi: 10.1126/sciadv.ado7464. Epub 2024 Aug 7. Sci Adv. 2024. PMID: 39110805 Free PMC article.
• Crosstalk between vault RNAs and innate immunity.
  Avila-Bonilla RG, Martínez-Montero JP. Avila-Bonilla RG, et al. Mol Biol Rep. 2024 Mar 5;51(1):387. doi: 10.1007/s11033-024-09305-y. Mol Biol Rep. 2024. PMID: 38443657 Free PMC article. Review.
• Generation of a new Adar1p150 -_/_- mouse demonstrates isoform-specific roles in embryonic development and adult homeostasis.
  Liang Z, Goradia A, Walkley CR, Heraud-Farlow JE. Liang Z, et al. RNA. 2023 Sep;29(9):1325-1338. doi: 10.1261/rna.079509.122. Epub 2023 Jun 8. RNA. 2023. PMID: 37290963 Free PMC article.
• The protein kinase R modifies gut physiology to limit colitis.
  Yim HCH, Chakrabarti A, Kessler S, Morimoto H, Wang D, Sooraj D, Ahmed AU, de la Motte C, Silverman RH, Williams BR, Sadler AJ. Yim HCH, et al. Front Immunol. 2023 Feb 17;14:1106737. doi: 10.3389/fimmu.2023.1106737. eCollection 2023. Front Immunol. 2023. PMID: 36875104 Free PMC article.
• Organellar homeostasis and innate immune sensing.
  Harapas CR, Idiiatullina E, Al-Azab M, Hrovat-Schaale K, Reygaerts T, Steiner A, Laohamonthonkul P, Davidson S, Yu CH, Booty L, Masters SL. Harapas CR, et al. Nat Rev Immunol. 2022 Sep;22(9):535-549. doi: 10.1038/s41577-022-00682-8. Epub 2022 Feb 23. Nat Rev Immunol. 2022. PMID: 35197578 Review.

References

1. 1. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3112-6 - PubMed
2. 1. FEBS Lett. 1977 Apr 1;76(1):1-10 - PubMed
3. 1. Nature. 1977 Aug 11;268(5620):540-2 - PubMed
4. 1. Nature. 1977 Aug 11;268(5620):537-40 - PubMed
5. 1. J Biol Chem. 1977 Jun 10;252(11):4007-10 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Europe PubMed Central
  • PubMed Central

• Other Literature Sources

  • The Lens - Patent Citations