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Regulation of Transcription of Na,K‐ATPase by G‐Protein Coupled Receptors: Involvement of Alternative Binding Partners
Author(s) -
Taub Mary,
Matlhagela Keikantse,
Borsick Maryann
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1044.12
Subject(s) - creb , prostaglandin e2 receptor , receptor , microbiology and biotechnology , chemistry , protein subunit , transcription factor , biology , biochemistry , gene , agonist
Transcription of Na,K‐ATPase alpha and beta subunit genes in renal cells is regulated by signaling initiated via G‐protein coupled receptors. Included amongst these receptors are the receptors for PGE 2 , the major renal prostaglandin. In the MDCK cell line PGE stimulates transcription of Na,K‐ATPase alpha and beta subunit genes. Transient transfection studies conducted in MDCK cells with a human Na,K‐ATPase β1 subunit promoter/luciferase construct, pHβ1–1141 Luc, indicate the PGE stimulation is mediated by EP1 receptors (coupled to phospholipase C) as well as EP2 and EP4 receptors (coupled to adenylate cyclase). A prostaglandin regulatory element (PGRE) within the β1 subunit promoter (−110 to −92, AGTCCCTGC) is sufficient to elicit a PGE 1 stimulation, although an alternative PGRE (TGACCTTC, −445 to −438) is also a site for regulation. In addition other G‐protein coupled receptors (e.g. dopamine) as well as ionic stress mediate regulation through PGREs. Evidence for CREB binding to these PGREs has been obtained. In addition, DNA affinity precipitation, electrophoretic mobility shift, and co‐immunoprecipitation studies indicate that in addition to CBP, Sp1 is an alternative binding partner for CREB. Transducers of regulated CREB activity TORCs) are other possible alternative binding partners in mediating regulation of Na,K‐ATPase transcription through PGREs.