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 G(i) 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 G(s) to G(i) may occur after receptor phosphorylation. This study supports a time-dependent biphasic cAMP response: an initial short G(s)-adenylate cyclase-mediated cAMP response is followed by receptor signal switching to a G(i)-PI3-kinase-mediated response.