Signal switching after stimulation of LGR7 receptors by human relaxin 2.
Previous studies have described a biphasic cAMP response after stimulation of LGR7 by human gene 2 (H2) relaxin, involving both adenylate cyclase and PI3-kinase activity. The current study identifies the upstream involvement of Gi in the PI3-kinase-mediated response, likely the result of receptor signal switching. Amino acid sequence analysis of the LGR7 C-terminal tail and intracellular loops revealed multiple putative phosphorylation sites, suggesting that signal switching from Gs to Gi may occur after receptor phosphorylation. This study supports a time-dependent biphasic cAMP response: an initial short Gs-adenylate cyclase-mediated cAMP response is followed by receptor signal switching to a Gi-PI3-kinase-mediated response.
Halls
Michelle L
ML
Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia.
Bathgate
Ross A
RA
Summers
Roger J
RJ
D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide; D012065:Relaxin / Q000378:metabolism*; D015398:Signal Transduction
D008565:Membrane Proteins; C095068:RLN2 protein, human; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin; D000242:Cyclic AMP; D020962:Heterotrimeric GTP-Binding Proteins