DREG, a developmentally regulated G protein-coupled receptor containing two conserved proteolytic cleavage sites.
We have identified and characterized a novel member of the G protein-coupled receptor (GPCR) family, termed DREG. DREG belongs to the LNB-TM7 subfamily and possesses a long amino-terminus that contains a CUB domain, a PTX domain, a hormone binding domain and a GPCR proteolytic site (GPS) domain. RT-PCR experiments and whole mount in situ hybridization in mice showed that DREG is expressed at high levels in the heart and somite during embryogenesis and in the adult lung. When DREG was transiently expressed in mammalian cultured cells, a 35-kD fragment was generated by endogenous proteolytic processing at the conserved GPS domain. This short fragment was found associated with the cell membrane, typical of GPCRs. DREG was further cleaved in the middle of the extracellular domain, generating a soluble 70-kD fragment containing the CUB and PTX domains. This processing was inhibited by an inhibitor of the endoprotease furin but not of matrix metalloproteinases. These results raise the possibility that DREG plays a role in development, not only as a receptor or an adhesion molecule but also as a secreted ligand.
Moriguchi
Tetsuo
T
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Haraguchi
Keiko
K
Ueda
Naoko
N
Okada
Masato
M
Furuya
Toshio
T
Akiyama
Tetsu
T
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D020224:Expressed Sequence Tags; D018507:Gene Expression Regulation, Developmental; D015894:Genome, Human; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010957:Plasmids; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D008024:Ligands; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; C103491:Reg-2 protein, Drosophila; D049452:Green Fluorescent Proteins