title: Tissue distribution and functional analyses of the constitutively active orphan G protein coupled receptors, GPR26 and GPR78.
abstract: GPR26 and GPR78 are orphan GPCRs (oGPCRs) that share 51% amino acid sequence identity and are widely expressed in selected tissues of the human brain as well as the developing and adult mouse brain. Investigation of the functional activity of GPR26 and GPR78 via expression in HEK293 cells showed that both proteins are constitutively active and coupled to elevated cAMP production. Accordingly, in yeast, GPR26 demonstrated apparent agonist-independent coupling to a chimeric Gpa1 protein in which the 5 C-terminal amino acids were from Galphas. A comparison of the proteins revealed an atypical glutamine residue in GPR78 in place of the conserved arginine residue (R3.50) in the so-called DRY box. Site-directed mutants R3.50 in GPR26 were constructed and retained their constitutive activity suggesting that these 2 receptors activate G proteins in a manner that is distinct from other group 1 GPCRs.
authors.affiliation: Neuroscience Discovery Research, Wyeth Research, CN8000, Princeton, NJ 08543, USA.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Jones
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Nawoschik
authors.forename: Kodangattil
authors.initials: K
authors.lastname: Sreekumar
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Uveges
authors.forename: Eugene
authors.initials: E
authors.lastname: Tseng
authors.forename: Lynn
authors.initials: L
authors.lastname: Zhang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Johnson
authors.forename: Lan
authors.initials: L
authors.lastname: He
authors.forename: Janet E
authors.initials: JE
authors.lastname: Paulsen
authors.forename: Brian
authors.initials: B
authors.lastname: Bates
authors.forename: Mark H
authors.initials: MH
authors.lastname: Pausch
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D000091342:Endoplasmic Reticulum Chaperone BiP; D044385:GTP-Binding Protein alpha Subunits / Q000096:biosynthesis / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C520707:G protein-coupled receptor GPR26, mouse; C489011:GPR26 protein, human; D044385:GTP-Binding Protein alpha Subunits; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; C084293:GPA1 protein, S cerevisiae; D043802:GTP-Binding Protein alpha Subunits, Gq-G11