Structure of the rat glucose-dependent insulinotropic polypeptide receptorgene

The Glucose-dependent insulinotropic polypeptide receptor (GIPR) is a membe r of the secretin-vasoactive intestinal polypeptide family of G-protein cou pled receptors possessing seven transmembrane domains. We report here the c loning and the exon-intron structure of the rat GIPR gene, along with the i dentification and characterization of its 5'-flanking region. The coding re gion of the GIPR gene spans approximately 10.2 kilobases and contains 13 ex ons. Three additional exons, two encoding either 5' or 3' untranslated sequ ences and one contained in a novel alternatively spliced mRNA, were identif ied. The 5'-flanking sequences contained a number of transcription factor b inding motifs, including a cAMP response element, an octamer binding site, three SP1 sites and an initiator element. However, neither a CAAT motif nor TATA box were found. Transient transfection assays demonstrated that the 5 '-flanking region of the GIPR gene can efficiently promote transcription in RIN38 cells and that deletion of 50 base pairs containing a potential SP1 binding sites leads to a 2.4-fold loss of transcriptional activity. In addi tion, transient transfection experiments comparing the relative promoter ac tivities of 5'-flanking sequences of the GIPR gene in RIN38 and rat-2 cells suggests that distal negative regulatory sequences may control cell-specif ic expression. (C) 1999 Elsevier Science Inc. All rights reserved.