Identification of an Orphan 7TM Receptor PSGR as a Functional Intracellular GPCR
Abstract
PSGR, a prostate‐specific orphan GPCR of olfactory family, expresses exclusively in the endoplasmic reticulum (ER) and Golgi network in surrogate cells including prostate cancer cells and normal human prostate epithelial cells. To determine if PSGR is functional or eventually goes to the cell surface we show here that removal of the N‐ and/or C‐terminal domains of PSGR, fusion of a signal peptide of EGF receptor to the N‐terminal of PSGR and/or tagging with various ER export motifs at the C‐terminal of PSGR failed to express the receptor on the cell surface unless they were coexpressed together with RPT1s, Ric8B, and Gαolf. Structural analysis revealed no obvious ER‐retention motif or any other structural determinants responsible for intracellular expression of PSGR. Surprisingly, PSGR inhibited p53 phosphorylation, but promoted Erk1/2 phosphorylation. Overexpression of the PSGR wild type, but not the mutant (D120A/R121L) incapable of coupling to G proteins and mutants with altered intracellular localization in CHO cells, promoted cell proliferation. These results suggest that PSGR is a functional intracellular GPCR and intact G protein signaling machineries are present in the intracellular organelles such as ER and Golgi. This work also suggest that PSGR may be constitutively active or the cognate ligand is likely intracellular and/or membrane permeable. Supported by USUHS startup funds to YHF
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2008
- Source ID
- 10.1096/fasebj.22.1_supplement.722.6
Entities
People
- Chen Sun
- Huaiyan Cheng
- Iswarduth Soojhawon
- Mi Wang
- Rongde Qiu
- Shiv Srivastava
- Ying‐hong Feng
Organizations
- Uniformed Services University of the Health Sciences