Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interferon-inducible double-stranded RNA-dependent protein kinase PKR has been suggested to function as a tumour suppressor gene product. Catalytically inactive mutants of PKR give rise to a tumorigenic phenotype when overexpressed in NIH-3T3 fibroblasts and this has been attributed to a dominant negative effect on the activity of the wild-type enzyme. Here we show that the mutant with Lys296 replaced by Arg, [K296R]PKR, not only inhibits the protein kinase activity of wild-type PKR but is also inhibitory towards another double-stranded RNA-dependent enzyme, the 40-kDa form of (2'-5')oligo(adenylate) synthetase. Inhibition of both wild-type PKR and (2'-5')oligo(adenylate) synthetase is reversed by adding higher concentrations of double-stranded RNA. These results suggest competition between [K296R]PKR and wild-type PKR or (2'-5')oligo(adenylate) synthetase for limiting amounts of double-stranded RNA. Moreover, the data imply that the tumorigenic effect of this PKR mutant could be due to inhibition of additional pathways requiring low levels of double-stranded RNA for activation and cannot be unambiguously attributed to inhibition of endogenous PKR itself.
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PMID:Regulation of the interferon-inducible protein kinase PKR and (2'-5')oligo(adenylate) synthetase by a catalytically inactive PKR mutant through competition for double-stranded RNA binding. 754 51

Recent evidence suggests that the human interferon-inducible double-stranded RNA-dependent protein kinase may function as a tumor suppressor. Here we describe the mapping of the gene for this kinase to chromosome region 2p21-22 by fluorescence in situ hybridization. A combined analysis of cytogenetic data from a series of 341 patients with hematologic disorders that exhibited cytogenetic abnormalities and from published reports indicates that abnormalities involving 2p21-22 occur nonrandomly and are observed among patients with acute myelogenous leukemia, raising the possibility of a role for this protein kinase in leukemogenesis.
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PMID:Mapping of the gene for interferon-inducible dsRNA-dependent protein kinase to chromosome region 2p21-22: a site of rearrangements in myeloproliferative disorders. 769 Nov 57

The levels and subcellular distribution of the interferon-inducible double-stranded RNA-dependent protein kinase PKR have been measured in human Daudi cells and stably transfected mouse NIH 3T3 cells expressing the human protein kinase. Immunofluorescence of intact cells and quantitative immunoblotting of cell extracts indicate that PKR occurs in both the cytoplasm and the cell nucleus, with staining specifically in the nucleolus. The ratio of cytoplasmic to nuclear PKR is approximately 5:1 in control cells; in response to interferon treatment the protein kinase is induced severalfold in the cytoplasm whereas the level in the nucleus does not increase significantly. Analysis of individual transfected cells by confocal microscopy reveals a pattern of distribution of PKR similar to that in Daudi cells, with immunostaining of cytoplasm and nucleoli. Similar results are observed whether cells expressing wild-type PKR or a catalytically inactive mutant form of the kinase are analyzed, but untransfected 3T3 cells are not stained by the antibody used. Two-dimensional isoelectric focusing analysis of PKR in whole cell extracts reveals the presence of multiple forms with different pI values whereas similar analysis of the nuclear fraction indicates only one predominant species with a relatively basic pI. These results suggest that PKR may have a role in the cell nucleus as well as the cytoplasm and that the subcellular distribution of the protein kinase may be related to post-translational modifications.
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PMID:Nuclear localization of the interferon-inducible protein kinase PKR in human cells and transfected mouse cells. 773 57