Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intracellular mechanism(s) underlying the upregulation of the hepatic Na+/taurocholate cotransporting polypeptide (ntcp) by prolactin (PRL) are unknown. In this report, we demonstrate a time-dependent increase in nuclear translocation of phosphorylated liver Stat5 (a member of the ignal ransducers and ctivators of ranscription family) that correlated with suckling-induced increases in serum PRL levels. In electrophoretic mobility gel shift assays, nuclear Stat5 exhibited specific DNA-binding ability towards IFN-gamma-activated sequence (GAS)-like elements (GLEs; 5'TTC/A-PyNPu-G/TAA-3') located in the -937 to -904 bp region of the ntcp promoter. Transient cotransfections in HepG2 cells revealed that PRL inducibility (2.5-3-fold) required coexpression of the long form of the PRL receptor (PRLRL) and Stat5. Deletion analysis mapped the PRLinducible region to -1237 to -758 bp of the ntcp promoter. Linking this 0.5-kb region to a heterologous thymidine kinase (tk) promoter, or linking multimerized ntcp GLEs either upstream of the ntcp minimal promoter (-158 to +47 bp) or the heterologous promoter conferred dose-dependent PRL responsiveness. The short form of the PRL receptor failed to transactivate ntcp GLEs. These results indicate that PRL acts via the PRLRL to facilitate Stat5 binding to ntcp-GLEs and to transcriptionally regulate ntcp.
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PMID:Regulation of the rat liver sodium-dependent bile acid cotransporter gene by prolactin. Mediation of transcriptional activation by Stat5. 918 14

Study of diverse PRL actions at a variety of fetal and maternal targets during pregnancy is complicated by receptor heterogeneity and multiple ligands circulating at this time. In the present studies, we have examined PRL receptors at a variety of potential targets by reverse transcription-PCR and Western analysis. Bovine tissues contain two different transcripts for the PRL receptor; the one that encodes a short form includes an additional 39 bases at a position identical to the deviation from the long form found in rodents and sheep. Western analyses of PRL receptors in microsomal fractions from various maternal and fetal tissues revealed considerable size heterogeneity. Collectively, the larger immunoreactive moieties (apparent Mr 100 kDa or greater) and the smaller species (47-55 kDa) correlated well with the relative abundance of the transcripts for the different forms of the receptor and varied considerably among tissues. N-Glycosylation was shown to be the major, but not the only, modification of both receptor forms when transiently transfected into COS-7 and END-6.2 cells. Much of the short form could be reduced to the mobility predicted from the complementary DNA by culture with tunicamycin; this was not true of the long form, suggesting modifications specific for its cytoplasmic domain. Differences in the pattern of immunoreactive species in the COS-7 and END-6.2 cells are consistent with cell-specific modifications. The ability of these receptor forms to mediate a transcriptional response to PRL and its placental relative, placental lactogen, was evaluated with a PRL response element inserted upstream from a thymidine kinase promoter/reporter gene construct transiently transfected into CHO-K1 cells. Both hormones were able to stimulate reporter gene expression through the long form, but not the short form, of the receptor. These studies will facilitate examination of tissue-specific actions of PRL and related hormones during pregnancy.
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PMID:Prolactin receptor heterogeneity in bovine fetal and maternal tissues. 923 67