Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interleukin-2 (IL-2) receptor gamma chain is an essential component of high and intermediate affinity IL-2 receptors (IL-2Rs), playing critical roles for ligand binding and internalization. We report here the isolation and characterization of the genomic locus for human IL-2R gamma, which, like IL-2R beta, is a member of the cytokine receptor superfamily. The IL-2R gamma gene is composed of eight exons and seven introns and spans approximately 4.2 kilobases. Analogous to the IL-2R beta gene, the two pairs of conserved cysteines typical of cytokine receptor superfamily proteins are located in adjacent exons, and the conserved WSXWS motif is located in the exon preceding the one that encodes the transmembrane domain and a small part of the cytoplasmic domain. In each gene, the remainder of the cytoplasmic domain is encoded by the final two exons. Southern blot analysis suggests that IL-2R gamma is encoded by a single copy gene. Cross-hybridizing sequences were detected in DNA derived from a number of other mammalian species but not from yeast. Primer extension analysis and ribonuclease protection assays revealed that there are three principal transcription initiation sites located 32-38 nucleotides 5' to the translation initiation AUG codon. These sites are upstream of the 5' end of the published IL-2R gamma cDNA sequence. The region 5' to the transcription initiation sites exhibited promoter activity when cloned upstream of the luciferase reporter gene. With this study, the organization of the genes encoding all three chains (alpha, beta, and gamma) of the IL-2 receptor has been determined and promoters for each identified.
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PMID:Characterization of the human interleukin-2 receptor gamma chain gene. 851 92

The PRL receptor (PRL-R) signals through the Janus tyrosine kinases (JAK) and other non-JAK tyrosine kinases, some of which are preassociated with the PRL-R. To clone PRL-R interacting proteins, the intracellular domain (ICD) of the long form of the PRL-R was used in a yeast two-hybrid screen of a human B cell cDNA library. One PRL-R interacting protein was identified as the 42-kDa form of the enzyme 2',5'-oligoadenylate synthetase (OAS). The in vivo interactions in yeast were further confirmed by an in vitro interaction assay and by coimmunoprecipitation in transfected mammalian cells. Functionally, OAS reduced the basal activity of two types of promoters in transiently transfected COS-1 cells. In the presence of PRL, OAS inhibited PRL induction of the immediate early IRF-1 (interferon-regulatory factor 1) promoter, but not PRL induction of the differentiation-specific beta-casein promoter, suggesting that OAS exerts specific effects on immediate early gene promoters. The inhibitory effects of OAS were accompanied by a reduction in PRL-inducible Stat1 (signal transducer and activator of transcription 1) DNA binding activity at the IRF-1 GAS (interferon-gamma-activated sequence) element. These results demonstrate a novel interaction of OAS with the PRL-R and suggest a role for OAS in modulating Stat1-mediated signaling to an immediate early gene promoter. Although previously characterized as a regulator of ribonuclease (RNase) L antiviral responses, OAS may have additional effects on cytokine receptor signal transduction pathways.
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PMID:Association of 2',5'-oligoadenylate synthetase with the prolactin (PRL) receptor: alteration in PRL-inducible stat1 (signal transducer and activator of transcription 1) signaling to the IRF-1 (interferon-regulatory factor 1) promoter. 1067 1

PRL has been reported to regulate fat metabolism in several species. We recently reported PRL receptor (PRLR) expression in mouse adipocytes and increased levels of PRLR expression in the adipose tissue of lactating and PRL-transgenic mice compared with controls. These results suggest PRLR-mediated effects in adipose tissue. However, to date most studies have been performed in vivo, and it is unclear whether PRL has direct effects on adipocytes. The PRLR belongs to the cytokine receptor family, and a family of suppressors of cytokine signaling (SOCS) was recently identified. The present study was performed to investigate whether PRL has direct effects on adipocytes. The expression of cytokine-inducible SH2-domain-containing protein (CIS), SOCS-3, and SOCS-2 mRNA and protein was analyzed using ribonuclease protection assay and immunoblotting, respectively. Ovine PRL induced CIS mRNA expression and a combination of oPRL and insulin induced SOCS-3 mRNA expression in adipocytes cultured in vitro for 0-240 min, demonstrating PRLR-mediated direct effects in these cells. Furthermore, CIS, SOCS-3, and SOCS-2 mRNA and protein were all transiently expressed in adipose tissue obtained from female mice stimulated with oPRL (1 microg/g BW) for 0-24 h. In adipose tissue of female mice with endogenously high PRL levels, PRL-transgenic mice, only SOCS-2 expression was increased. The level of SOCS-2 mRNA was also increased in adipose tissue during pregnancy and lactation compared with that in wild-type virgin female mice. A possible reason for increased SOCS-2 expression after prolonged PRL exposure during lactation and in the PRL transgenes could be to restore the sensitivity of adipose tissue to PRL. In addition, the direct effect of PRL on leptin production was investigated in adipocytes cultured in vitro for 6 h. PRL inhibited insulin-induced leptin production in vitro. However, PRL had no effect on leptin production in the absence of insulin. In contrast, serum leptin concentrations were increased in PRL-transgenic females compared with control mice. In conclusion, our results demonstrate functional PRLRs in mouse adipocytes and suggest a role for CIS, SOCS-3, and SOCS-2 in regulating PRL signal transduction in adipose tissue.
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PMID:PRL receptor-mediated effects in female mouse adipocytes: PRL induces suppressors of cytokine signaling expression and suppresses insulin-induced leptin production in adipocytes in vitro. 1160 56