Molecular cloning and characterization of a novel retinoic acid-inducible gene that encodes a putative G protein-coupled receptor

The effects of retinoids such as all-trans-retinoic acid (ATRA) on cell gro wth, differentiation, and apoptosis are thought to be mediated by nuclear r etinoid receptors, which are involved in ligand-dependent transcriptional a ctivation of target genes. Using differential display, we identified the cD NA of a novel gene, designated retinoic acid-inducible gene 1 (RAIG1), whic h was induced by ATRA in the squamous carcinoma cell line UMSCC-22B, Two RA IG1 transcripts of 2.4 and 6.8 kilobase pairs, respectively, have the same ORF that encodes a 357-amino acid polypeptide. RAIG1 mRNA is expressed at h igh level in fetal and adult lung tissues. Induction of RAIG1 expression by ATRA is rapid (within 2 h) and dose-dependent in the range between 1 nM to 1 mu M. The constitutive RAIG1 mRNA levels, which were low in three of fiv e head and neck and four of six lung cancer cell lines, increased after ATR A treatment in most cell lines. The deduced RAIG1 protein sequence contains seven transmembrane domains, characteristic of G protein-coupled receptors , A fusion protein of RAIG1 and the green fluorescent protein was localized in the cell surface membrane and perinuclear vesicles in transiently trans fected cells. RAIG1 was mapped to chromosome 12p12.3-p13, Our results provi de novel evidence for a possible interaction between retinoid and G protein signaling pathways.