Regulation of Interferon-Induced Protein Kinase PKR: Modulation of P58IPK Inhibitory Function by a Novel Protein, P52rIPK

摘要: The cellular response to environmental signals is largely dependent upon the induction of responsive protein kinase signaling pathways. Within these pathways, distinct protein-protein interactions play a role in determining specificity through regulation function. interferon-induced serine/threonine kinase, PKR, activated various stimuli. Like many kinases, PKR regulated direct with activator and inhibitory molecules, including P58IPK, inhibitor. P58IPK functions represses PKR-mediated phosphorylation eukaryotic initiation factor 2α subunit (eIF-2α) interaction, thereby relieving PKR-imposed block on mRNA translation cell growth. To further define molecular mechanism underlying we have utilized an interaction cloning strategy identify novel cDNA encoding P58IPK-interacting protein. This protein, designated P52rIPK, possesses limited homology charged domain Hsp90 expressed wide range lines. P52rIPK interacted yeast two-hybrid assay were recovered as complex from mammalian extracts. When coexpressed yeast, repressed eIF-2α phosphorylation, inhibiting normally toxic growth-suppressive effects associated Conversely, introduction into strains resulted restoration both activity concomitant growth suppression due inhibition Furthermore, inhibited function reconstituted vitro PKR-regulatory assay. Our results demonstrate that which, turn, upregulation activity. Taken together, our data describe kinase-regulatory system which encompasses intersection interferon-, stress-, growth-regulatory