THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN-KINASE INDUCED BY INTERFERON - DSRNA-PK
THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN-KINASE INDUCED BY INTERFERON - DSRNA-PK
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DOI：
10.1089/jir.1989.9.641
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发表时间：
1989-12-01
期刊：
影响因子：
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通讯作者：
HOVANESSIAN, AG
中科院分区：
文献类型：
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作者：
HOVANESSIAN, AG
Early observations on the inhibitory action of double-stranded (ds) RNA in cell-free systems'1-5'were the basis for the discovery of the two dsRNA-activated enzymes in interferon (IFN)-treated cells: the 2', 5'oligoadenylate (2-5A) synthetase and the protein kinase.'6" 14'Analogous enzymes were also found in rabbit reticulocytes, in different tissues of mouse, and in human peripheral blood mononuclear cells.'15" 23'Here, I willdiscuss some recent developments in the field of the protein kinase. The dsRNA-activated protein kinase (dsRNA-PK) has been first described according to its activity which is highly enhanced in mouse and human cells following treatment with IFN. In the presence of dsRNA such activity is manifested by the phosphorylation of a 65 to 67-kD protein (p65) in mouse cells or a 68 to 72-kD protein (p68) in human cells. The function of the dsRNA-PK is correlated with the phosphorylation of the a-subunit of the protein initiation factor, IF2, thus mediating an inhibition of initiation of protein synthesis. The protein kinase activity is independent of cAMP or cGMP and is markedly stimulated by manganese. It phosphorylates p65 and p68 on serine and threonine residues.'24'25'The p65 and p68 are associated with the rough microsomal pellet from which they could be recovered efficiently by treatment with 0.5 M NaCl or KC1 and 1% nonionic detergent.Another protein kinase associated with the heme-regulated inhibitor (HCR) can also phosphorylate IF2.'15> Thus, phosphorylation of the a-subunit of IF2 can be catalyzed by two different protein kinases, both of which, however, phosphorylate the same peptide on IF2.'24'26'To rule out any misunderstanding, the dsRNA-activated protein kinase should not be referred to as IF2-kinase as has been done previously. The kinase has also been referred to as dsRNA-activated inhibitor (DAI). Once again this is misleading, because the kinase itself is not the inhibitory agent.
