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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | May, W. S. Jagus, R. Ito, T. |
| Description | Author Affiliation: Ito T ( Johns Hopkins Oncology Center, Baltimore, MD 21231.); |
| Abstract | In a murine interleukin 3 (IL-3)-dependent cell line, IL-3 deprivation resulted in increased autophosphorylation of double-stranded RNA-dependent protein kinase (PKR) that has been reported to inhibit protein synthesis by phosphorylating the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha). Autophosphorylation was characterized by a shift up in mobility of PKR on SDS/PAGE gels from a 60- to a 64-kDa form. In vitro kinase studies comparing the autophosphorylated 64-kDa PKR with the nonphosphorylated 60-kDa PKR confirmed that only the 64-kDa form was active for eIF-2 alpha phosphorylation. PKR activation in vivo was associated with phosphorylation of eIF-2 alpha and inhibition of protein synthesis. Addition of IL-3 to deprived cells elicited a reciprocal response characterized by the rapid dephosphorylation of PKR and eIF-2 alpha, indicating inactivation of PKR. This was rapidly followed by the full recovery of protein synthesis. Furthermore, upon IL-3 addition, a 97-kDa phosphotyrosine-containing protein becomes rapidly and transiently associated with PKR prior to dephosphorylation of PKR and eIF-2 alpha. Genistein, a tyrosine kinase inhibitor, blocks both phosphorylation of the 97-kDa phosphoprotein and protein synthesis after IL-3 addition, suggesting a role for the 97-kDa phosphoprotein in the mechanism of inactivation of PKR and stimulation of protein synthesis. Thus, IL-3 appears to positively regulate protein synthesis by inducing the inactivation of PKR in a growth factor signaling pathway. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 16 |
| Volume Number | 91 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1994-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Eukaryotic Initiation Factor-2 Metabolism Gene Expression Regulation, Enzymologic Drug Effects Interleukin-3 Pharmacology Protein Biosynthesis Protein-Serine-Threonine Kinases Animals Cells, Cultured Genistein Isoflavones Mice Phosphoproteins Phosphorylation Phosphotyrosine Protein-Tyrosine Kinases Antagonists & Inhibitors Tyrosine Analogs & Derivatives EIF-2 Kinase Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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