Disease relevance of PROKR1

• Stress conditions such as serum withdrawal, TNF-alpha, and hypoxia markedly increased PK-R2 expression, whereas mRNA levels of PK-R1 remained unchanged [1].
• Replication of hepatitis C virus (HCV) RNA in mouse embryonic fibroblasts: protein kinase R (PKR)-dependent and PKR-independent mechanisms for controlling HCV RNA replication and mediating interferon activities [2].
• Replication of the m142 and m143 knockout mutants was partially restored by expression of the human cytomegalovirus TRS1 gene, a known double-stranded-RNA-binding protein that inhibits PKR activation [3].
• In this study, normal human foreskin keratinocytes (NHKs) transfected stably with the HPV 31 or 16 genomes and cell lines expressing the HPV 16 E6 and E7 oncoproteins were used to examine effects on the PKR pathway [4].
• BACKGROUND AND OBJECTIVE: A partial red blood cell (RBC) pyruvate-kinase (PK-R) deficiency was found in a patient with concomitant hereditary spherocytosis (HS) and chronic hemolytic anemia [5].

High impact information on PROKR1

• Global protein synthesis was impaired in these cells, which correlated with phosphorylation of the double-stranded RNA-dependent protein kinase R (PKR) and its target protein, the eukaryotic translation initiation factor 2alpha, suggesting that m142 and m143 are necessary to block the PKR-mediated shutdown of protein synthesis [3].
• PKR, an interferon-induced double-stranded RNA activated serine-threonine kinase, is a component of signal transduction pathways mediating cell growth control and responses to stress and viral infection [6].
• In this report, we show that PKs not only stimulate Ca(2+) mobilization but also induce cAMP accumulation in PKR-expressing cells [7].
• There was no temporal variation in expression of PK2, PKR1, or PKR2 [8].
• The displacement of specific binding by GTP gamma S suggests that the prokineticin receptor may belong to the family of G protein-coupled receptors [9].

Biological context of PROKR1

• PK-R1, locating in chromosome 2, and PK-R2, locating in chromosome 20p13, shared 87% homology, which was an extremely high value among known GPCRs [10].
• Tissue distribution analysis revealed that expression of PK-R1 was observed in the testis, medulla oblongata, skeletal muscle and skin, while that of PK-R2 showed preferential expression in the central nervous system [10].
• Non-isotopic in situ hybridisation and radiation hybrid mapping have identified GPR72 to be localised on human chromosome 11q21.1, and GPR73 on human chromosome 2p14 [11].
• Inhibition of PKR significantly inhibited apoptosis induction by Ad.mda-7 when administered alone but not when used in combination with gefitinib [12].
• However, levels of phosphorylated PKR were decreased 4-fold through a post-transcriptional mechanism mediated by E6 and E7 that was independent of the transcriptional downregulation mediated by HPV [4].

Anatomical context of PROKR1

• Subsequent expression analyses on the EG-VEGF receptors showed that hPK-R1 and hPK-R2 are differentially expressed in human endometrium, but show no significant correlation with the hormonal treatments [13].
• Interestingly, also EC from brain capillaries (BCEC) expressed only PK-R1 [14].
• Corpus luteum (CL)-derived EC (LEC) expressed both PK-R1 and PK-R2 [14].
• However, GPR73 mRNA can be found in heart, skeletal muscle and pancreas [11].
• Pyruvate kinase PK-R1, predominant in the erythroblasts and the young red cells, is composed of four identical L' subunits [15].

Associations of PROKR1 with chemical compounds

• PK-R1 and PK-R2 were found in NPEC, EPN, and CPEC [16].
• We investigated whether ceramide influences articular chondrocyte matrix homeostasis and, if so, the role of PKR in this process [17].
• To inhibit PKR, 2-aminopurine was added to duplicate cultures [17].

Physical interactions of PROKR1

• Prokineticins (PKs), multifunctional secreted proteins, activate two endogenous G protein-coupled receptors (R) termed PK-R1 and PK-R2 [14].

Analytical, diagnostic and therapeutic context of PROKR1

• Y-receptor-like genes GPR72 and GPR73: molecular cloning, genomic organisation and assignment to human chromosome 11q21.1 and 2p14 and mouse chromosome 9 and 6 [11].
• PKR also accumulated in the nucleus during HCMV infection as determined by indirect immunofluorescence and immunoblot analysis [18].
• Analysis of separate PKR functional domains by NMR and X-ray crystallography has revealed details of PKR RNA binding domains and kinase domain, respectively [6].

References