Genomes and Genes
Summary: Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells.
- Prosser H, Bradley A, Chesham J, Ebling F, Hastings M, Maywood E. Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei. Proc Natl Acad Sci U S A. 2007;104:648-53 pubmed
- Scobie H, Wigelsworth D, Marlett J, Thomas D, Rainey G, Lacy D, et al. Anthrax toxin receptor 2-dependent lethal toxin killing in vivo. PLoS Pathog. 2006;2:e111 pubmed..Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis. ..
- Xu Q, Hesek E, Zeng M. Transcriptional stimulation of anthrax toxin receptors by anthrax edema toxin and Bacillus anthracis Sterne spore. Microb Pathog. 2007;43:37-45 pubmed..These results suggest that anthrax edema toxin and B. anthracis Sterne spore are involved in the ANTXR mRNA regulation in host cells. ..
- Su Z, Cao L, Zhu Y, Liu X, Huang Z, Huang A, et al. Nogo enhances the adhesion of olfactory ensheathing cells and inhibits their migration. J Cell Sci. 2007;120:1877-87 pubmed..Taken together, we demonstrate, for the first time, that Nogo, a myelin-associated inhibitor of axon regeneration in the CNS, enhances the adhesion and inhibits the migration of OECs via NgR regulation of RhoA. ..
- Shan S, Chandrasekar S, Walter P. Conformational changes in the GTPase modules of the signal reception particle and its receptor drive initiation of protein translocation. J Cell Biol. 2007;178:611-20 pubmed..Most importantly, our results show that an elaborate rearrangement within the SRP-SR GTPase complex is required to drive the unloading and initiate translocation of cargo proteins. ..
- Shan S, Schmid S, Zhang X. Signal recognition particle (SRP) and SRP receptor: a new paradigm for multistate regulatory GTPases. Biochemistry. 2009;48:6696-704 pubmed publisher..We suggest that these multistate regulatory GTPases are uniquely suited to provide spatial and temporal control of complex cellular pathways that require multiple molecular events to occur in a highly coordinated fashion. ..
- Liu S, Crown D, Miller Randolph S, Moayeri M, Wang H, Hu H, et al. Capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo. Proc Natl Acad Sci U S A. 2009;106:12424-9 pubmed publisher..Finally, the CMG2-null mice are also shown to be highly resistant to B. anthracis spore infection, attesting to the importance of both anthrax toxin and CMG2 in anthrax infections. ..
- Reyes C, Rutenber E, Walter P, Stroud R. X-ray structures of the signal recognition particle receptor reveal targeting cycle intermediates. PLoS ONE. 2007;2:e607 pubmed..We propose that these structural changes represent discrete conformational states assumed by FtsY during targeting complex formation and dissociation. ..
- Mesbah K, Camus A, Babinet C, Barra J. Mutation in the Trapalpha/Ssr1 gene, encoding translocon-associated protein alpha, results in outflow tract morphogenetic defects. Mol Cell Biol. 2006;26:7760-71 pubmed
- Zhang X, Kung S, Shan S. Demonstration of a multistep mechanism for assembly of the SRP x SRP receptor complex: implications for the catalytic role of SRP RNA. J Mol Biol. 2008;381:581-93 pubmed publisher..This provides a coherent model that explains how the 4.5S RNA exerts its catalytic role in SRP x SR complex assembly. ..
- Egea P, Tsuruta H, De Leon G, Napetschnig J, Walter P, Stroud R. Structures of the signal recognition particle receptor from the archaeon Pyrococcus furiosus: implications for the targeting step at the membrane. PLoS ONE. 2008;3:e3619 pubmed publisher..Based on previous structures of two sub-complexes, we propose a model of the core of archeal and eukaryotic SRP*SR targeting complexes...
- Bradshaw N, Neher S, Booth D, Walter P. Signal sequences activate the catalytic switch of SRP RNA. Science. 2009;323:127-30 pubmed publisher..Thus, SRP RNA is a molecular switch that renders the SRP-SR GTPase engine responsive to signal peptide recruitment, coupling GTP hydrolysis to productive protein targeting. ..
- Callander G, Thomas W, Bathgate R. Prolonged RXFP1 and RXFP2 signaling can be explained by poor internalization and a lack of beta-arrestin recruitment. Am J Physiol Cell Physiol. 2009;296:C1058-66 pubmed publisher..The apparent lack of classical regulation for RXFP1 and RXFP2 provides the molecular basis for the prolonged signaling and physiological actions of relaxin and related peptides. ..
- Samuel C, Lin F, Hossain M, Zhao C, Ferraro T, Bathgate R, et al. Improved chemical synthesis and demonstration of the relaxin receptor binding affinity and biological activity of mouse relaxin. Biochemistry. 2007;46:5374-81 pubmed..05 vs untreated group), consistent with the actions of H2 relaxin. These combined data demonstrate that mouse relaxin can effectively inhibit collagen deposition and accumulation (fibrosis) over long-term treatment periods. ..
- Weiche B, Bürk J, Angelini S, Schiltz E, Thumfart J, Koch H. A cleavable N-terminal membrane anchor is involved in membrane binding of the Escherichia coli SRP receptor. J Mol Biol. 2008;377:761-73 pubmed publisher..These data suggest that membrane binding and function of FtsY are in part regulated by proteolytic cleavage of the conserved 14-amino-acid motif. ..
- Scott D, Layfield S, Yan Y, Sudo S, Hsueh A, Tregear G, et al. Characterization of novel splice variants of LGR7 and LGR8 reveals that receptor signaling is mediated by their unique low density lipoprotein class A modules. J Biol Chem. 2006;281:34942-54 pubmed..This study highlights the essential role of the LDLa module in LGR7 and LGR8 function and introduces a novel model of GPCR regulation. ..
- Zhang X, Schaffitzel C, Ban N, Shan S. Multiple conformational switches in a GTPase complex control co-translational protein targeting. Proc Natl Acad Sci U S A. 2009;106:1754-9 pubmed publisher..Thus, the SRP and SR GTPases, without recruiting external regulatory factors, constitute a self-sufficient system that provides exquisite spatial and temporal control of a complex cellular process. ..
- van der Goot G, Young J. Receptors of anthrax toxin and cell entry. Mol Aspects Med. 2009;30:406-12 pubmed publisher..The roles played by cellular factors in regulating the endocytosis of toxin-receptor complexes is also discussed. ..
- Kong R, Shilling P, Lobb D, Gooley P, Bathgate R. Membrane receptors: structure and function of the relaxin family peptide receptors. Mol Cell Endocrinol. 2010;320:1-15 pubmed publisher..contrast, relaxin-3 and INSL5 interact with another class of type I GPCRs which lack a large ectodomain, the peptide receptors GPCR135 and GPCR142, respectively...
- Stengel K, Holdermann I, Wild K, Sinning I. The structure of the chloroplast signal recognition particle (SRP) receptor reveals mechanistic details of SRP GTPase activation and a conserved membrane targeting site. FEBS Lett. 2007;581:5671-6 pubmed..In cpFtsY this motif is extended, which might be responsible for the enhanced attachment of the protein to the thylakoid membrane. ..
- Halls M, van der Westhuizen E, Bathgate R, Summers R. Relaxin family peptide receptors--former orphans reunite with their parent ligands to activate multiple signalling pathways. Br J Pharmacol. 2007;150:677-91 pubmed..Studies of the distribution and function of RXFP3 suggest that it is a potential target for anti-anxiety and anti-obesity drugs. ..
- Van der Westhuizen E, Halls M, Samuel C, Bathgate R, Unemori E, Sutton S, et al. Relaxin family peptide receptors--from orphans to therapeutic targets. Drug Discov Today. 2008;13:640-51 pubmed publisher..Several of them are the cognate ligands for 4 G-protein-coupled relaxin family peptide receptors (RXFPs; formerly LGR7, LGR8, GPCR135, GPCR142)...
- Ramachandran V, Arumugam T, Hwang R, Greenson J, Simeone D, Logsdon C. Adrenomedullin is expressed in pancreatic cancer and stimulates cell proliferation and invasion in an autocrine manner via the adrenomedullin receptor, ADMR. Cancer Res. 2007;67:2666-75 pubmed..These data indicate that adrenomedullin acting via ADMR increases the aggressiveness of pancreatic cancer cells and suggests that these molecules may be useful therapeutic targets. ..
- Bennett R, Dalton S, Mahan K, Gentry Nielsen M, Hamel F, Tuma D. Relaxin receptors in hepatic stellate cells and cirrhotic liver. Biochem Pharmacol. 2007;73:1033-40 pubmed..Cirrhosis also caused increased expression of both receptors. Therefore, agents that stimulate LGR8 and LGR7 may be therapeutically useful to limit the activation of hepatic stellate cells in liver injury. ..
- Chandrasekar S, Chartron J, Jaru Ampornpan P, Shan S. Structure of the chloroplast signal recognition particle (SRP) receptor: domain arrangement modulates SRP-receptor interaction. J Mol Biol. 2008;375:425-36 pubmed
- Halls M, Van der Westhuizen E, Wade J, Evans B, Bathgate R, Summers R. Relaxin family peptide receptor (RXFP1) coupling to G(alpha)i3 involves the C-terminal Arg752 and localization within membrane Raft Microdomains. Mol Pharmacol. 2009;75:415-28 pubmed publisherThe relaxin family peptide receptors (RXFP) 1 and 2 are targets for the relaxin family peptides relaxin and insulin-like peptide 3 (INSL3), respectively...
- Hossain M, Rosengren K, Haugaard Jönsson L, Zhang S, Layfield S, Ferraro T, et al. The A-chain of human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors. J Biol Chem. 2008;283:17287-97 pubmed publisher..Our results provide new insights into the action of relaxins and demonstrate that the role of the A-chain for relaxin activity is both peptide- and receptor-dependent. ..
- Rubio A, Jiang X, Pogliano K. Localization of translocation complex components in Bacillus subtilis: enrichment of the signal recognition particle receptor at early sporulation septa. J Bacteriol. 2005;187:5000-2 pubmed..These results suggest FtsY delivers secreted proteins to SecYEG at the septum, consistent with initial septal localization of forespore membrane proteins. ..
- Schulz S, Hyslop T, Haaf J, Bonaccorso C, Nielsen K, Witek M, et al. A validated quantitative assay to detect occult micrometastases by reverse transcriptase-polymerase chain reaction of guanylyl cyclase C in patients with colorectal cancer. Clin Cancer Res. 2006;12:4545-52 pubmed..This validated assay is being applied to approximately 10,000 lymph nodes in a prospective trial to define the sensitivity of GCC qRT-PCR for staging patients with colorectal cancer. ..
- Spanggord R, Siu F, Ke A, Doudna J. RNA-mediated interaction between the peptide-binding and GTPase domains of the signal recognition particle. Nat Struct Mol Biol. 2005;12:1116-22 pubmed..The orientation of the RNA suggests how peptide binding and GTP hydrolysis can be coupled through direct structural contact during cycles of SRP-directed protein translocation. ..
- Hoffmann P, Feige J, Alfaidy N. Expression and oxygen regulation of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy. Endocrinology. 2006;147:1675-84 pubmed..The expression pattern of EG-VEGF, its regulation by oxygen tension, and its complementary localization to that of VEGF suggest that this new factor might also be deregulated in preeclampsia. ..
- Pasquali D, Rossi V, Staibano S, De Rosa G, Chieffi P, Prezioso D, et al. The endocrine-gland-derived vascular endothelial growth factor (EG-VEGF)/prokineticin 1 and 2 and receptor expression in human prostate: Up-regulation of EG-VEGF/prokineticin 1 with malignancy. Endocrinology. 2006;147:4245-51 pubmed..Thus, the level of EG-VEGF/PK1 could be useful for prostate cancer outcome evaluation and as a target for prostate cancer treatment in the future. ..
- Bathgate R, Ivell R, Sanborn B, Sherwood O, Summers R. Receptors for relaxin family peptides. Ann N Y Acad Sci. 2005;1041:61-76 pubmed
- Ivell R, Hartung S, Anand Ivell R. Insulin-like factor 3: where are we now?. Ann N Y Acad Sci. 2005;1041:486-96 pubmed..It is also an indicator of differentiation status not only for Leydig cells but also for the theca interna cells of the ovary. ..
- Matsumoto S, Yamazaki C, Masumoto K, Nagano M, Naito M, Soga T, et al. Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2. Proc Natl Acad Sci U S A. 2006;103:4140-5 pubmed..Our current findings demonstrated that physiological activation of PKR2 is essential for normal development of the OB and sexual maturation...
- Andreev I, Danilevich V, Grishin E. [Alternative splicing of pre-mRNA encoding the Musca domestica latrophilin-like protein(LLP): primary structures of four spliced forms of mRNA and their protein products]. Bioorg Khim. 2005;31:175-85 pubmed..The limitations and drawbacks of the existing 3'-RACE techniques found during study of the long alternatively spliced cDNAs are analyzed, and ways for overcoming these difficulties are proposed. ..
- Scott D, Tregear G, Bathgate R. LGR7-truncate is a splice variant of the relaxin receptor LGR7 and is a relaxin antagonist in vitro. Ann N Y Acad Sci. 2005;1041:22-6 pubmed..Expression of LGR7-Truncate with LGR7 in HEK-293T cells resulted in decreased relaxin-induced signaling of LGR7. LGR7-Truncate is potentially an endogenous regulator of LGR7 signaling. ..
- Halic M, Beckmann R. The signal recognition particle and its interactions during protein targeting. Curr Opin Struct Biol. 2005;15:116-25 pubmed..On this basis, the first structure-based models can be suggested that explain important aspects of protein targeting, such as the SRP-ribosome and SRP-SR interactions. ..
- Rainey G, Wigelsworth D, Ryan P, Scobie H, Collier R, Young J. Receptor-specific requirements for anthrax toxin delivery into cells. Proc Natl Acad Sci U S A. 2005;102:13278-83 pubmed..Our results suggest that toxin can form pores at different points in the endocytic pathway, depending on which receptor is used for entry. ..
- Bathgate R, Ivell R, Sanborn B, Sherwood O, Summers R. International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides. Pharmacol Rev. 2006;58:7-31 pubmed..peptide 3 (LGR8), relaxin-3 (GPCR135), and insulin-like peptide 5 (LGPCR142) be named the relaxin family peptide receptors 1 through 4 (RXFP1-4)...
- Schwartz T, Schmidt D, Brohawn S, Blobel G. Homodimerization of the G protein SRbeta in the nucleotide-free state involves proline cis/trans isomerization in the switch II region. Proc Natl Acad Sci U S A. 2006;103:6823-8 pubmed..The switch mechanism involves cis/trans isomerization of a strictly conserved proline, potentially implying a new layer of regulation of cotranslational transport. ..
- Halic M, Gartmann M, Schlenker O, Mielke T, Pool M, Sinning I, et al. Signal recognition particle receptor exposes the ribosomal translocon binding site. Science. 2006;312:745-7 pubmed
- Bathgate R, Lin F, Hanson N, Otvos L, Guidolin A, Giannakis C, et al. Relaxin-3: improved synthesis strategy and demonstration of its high-affinity interaction with the relaxin receptor LGR7 both in vitro and in vivo. Biochemistry. 2006;45:1043-53 pubmed..The activity of the peptide was tested against relaxin family peptide receptors. Although the highest activity was demonstrated on the human relaxin-3 receptor (GPCR135), the peptide also ..
- Halls M, Bathgate R, Summers R. Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms. Mol Pharmacol. 2006;70:214-26 pubmed..Differences in cAMP accumulation stem from the ability of RXFP1 to recruit coupling to Galphai3, release G-betagamma subunits and thus activate a delayed PI3K-PKCzeta pathway to further increase cAMP accumulation. ..
- Bennett R, Mahan K, Gentry Nielsen M, Tuma D. Relaxin receptor expression in hepatic stellate cells and in cirrhotic rat liver tissue. Ann N Y Acad Sci. 2005;1041:185-9 pubmed..In conclusion, both LGR7 and LGR8 are expressed in activated HSCs and cirrhotic liver, suggesting that relaxin, InsL3, or relaxin-3 may be useful in the treatment of hepatic fibrosis. ..
- Samuel C, Du X, Bathgate R, Summers R. 'Relaxin' the stiffened heart and arteries: the therapeutic potential for relaxin in the treatment of cardiovascular disease. Pharmacol Ther. 2006;112:529-52 pubmed..It is becoming increasingly clear that relaxin has a number of diverse physiological and pathological roles in the cardiovascular system that may have important therapeutic and clinical implications. ..
- Scott D, Fu P, Shen P, Gundlach A, Layfield S, Riesewijk A, et al. Characterization of the rat INSL3 receptor. Ann N Y Acad Sci. 2005;1041:13-6 pubmed..LGR8 mRNA expression was demonstrated in the gubernaculum at the time of testis descent and in the testis associated with germ cells. ..
- Scobie H, Thomas D, Marlett J, Destito G, Wigelsworth D, Collier R, et al. A soluble receptor decoy protects rats against anthrax lethal toxin challenge. J Infect Dis. 2005;192:1047-51 pubmed..Stoichiometric concentrations of sCMG2 protect rats against lethal toxin challenge, making sCMG2 one of the most effective anthrax antitoxins described to date. ..
- Yang Y, Zhou L, Liu S, Tang J, Li F, Li R, et al. Expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in control of GnRH secretion. Acta Pharmacol Sin. 2005;26:976-81 pubmedTo investigate the expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in the control of GnRH secretion...
- Cheng M, Leslie F, Zhou Q. Expression of prokineticins and their receptors in the adult mouse brain. J Comp Neurol. 2006;498:796-809 pubmed..These extensive expression patterns suggest that prokineticins may have a broad array of functions in the central nervous system, including circadian rhythm, neurogenesis, ingestive behavior, reproduction, and autonomic function. ..