Mechanism of interferon action: phosphorylation of protein synthesis initiation factor eIF-2 in interferon-treated human cells by a ribosome-associated kinase processing site specificity similar to hemin-regulated rabbit reticulocyte kinase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 76 ·No. 2 ·1979-02-00 ·Pages 600-4

Samuel CE

Abstract

The phosphorylation of purified protein synthesis factors catalyzed by protein kinase preparations isolated from interferon-treated human amnion cells was examined. Ribosomal salt-wash fractions prepared from interferon-treated human cells contained a protein kinase that catalyzed the [gamma-(32)P]ATP-mediated phosphorylation of the 38,000-dalton subunit of eukaryotic initiation factor 2 (eIF-2alpha); this kinase activity was significantly enhanced in interferon-treated as compared to untreated cells. The tryptic [(32)P]phosphopeptide pattern obtained for eIF-2alpha phosphorylated by the interferon-mediated human kinase was indistinguishable from the pattern obtained for eIF-2alpha phosphorylated by the hemin-regulated rabbit reticulocyte kinase when analyzed by thin-layer chromatography with three different solvent systems and by high-voltage electrophoresis. O-[(32)P]Phosphoserine was liberated by partial acid hydrolysis from eIF-2alpha phosphorylated by either the human or the rabbit kinase. In addition to the phosphorylation of eIF-2alpha, interferon treatment of human cells enhanced the phosphorylation of two additional ribosome-associated proteins designated P(1) and P(f). The major phosphoester linkage observed for the human, as well as murine, phosphoprotein P(1) was O-phosphoserine. The interferon-mediated phosphorylation of both eIF-2alpha and protein P(1) was dependent upon the presence of RNA with double-stranded character; P(f) phosphorylation was not affected by double-stranded RNA. These results suggest that the interferon-mediated ribosome-associated human protein kinase catalyzes the phosphorylation of eIF-2alpha in a site-specific manner that is apparently identical with the reaction catalyzed by the hemin-regulated rabbit reticulocyte kinase; hence, the phosphorylation of eIF-2 may play a role in regulating the initiation of translation in interferon-treated cells.

MeSH Terms

Cells, Cultured Hemin/pharmacology Humans Interferons/pharmacology Peptide Chain Initiation, Translational/drug effects Peptide Initiation Factors/metabolism Phosphorylation Protein Kinases/metabolism RNA/pharmacology RNA, Messenger/metabolism RNA, Viral/metabolism Reticulocytes/enzymology Ribosomes/enzymology

Chemicals

Peptide Initiation Factors RNA, Messenger RNA, Viral RNA Hemin Interferons Protein Kinases

Authors & Affiliations

1 authors, click to expand affiliations / ORCID

Samuel C E

References (40)

40 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.76.2.600

Published

1979-02-00

Pages

600-4

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC382996

Subset

External Links

PubMed source DOI: 10.1073/pnas.76.2.600 PMC Full Text View journal details

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Mechanism of interferon action: phosphorylation of protein synthesis initiation factor eIF-2 in interferon-treated human cells by a ribosome-associated kinase processing site specificity similar to hemin-regulated rabbit reticulocyte kinase.

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