Human phosphatidylethanolamine-binding protein facilitates heterotrimeric G protein-dependent signaling

In this study we report that human phosphatidylethanolamine-binding protein (hPBP) facilitates heterotrimeric G protein-coupled signaling. In Xenopus laevis oocytes, coexpression of hPBP with human mu opioid receptor, human d elta opioid receptor, or human somatostatin receptor 2 evoked an agonist-in duced increase in potassium conductance of G protein-activated inwardly rec tifying potassium channels. This activation of heterotrimeric G protein sig naling in oocytes could also be elicited by injection of bacterially overex pressed and purified hPBP. Stimulatory effect was pertussis toxin-sensitive and present even in the absence of coexpressed receptors. Additionally, an increase in G protein-mediated inhibition of adenylate cyclase activity, m easured by the inhibition of forskolin-mediated cAMP accumulation, could be detected in HEK293 and NIH3T3 cells after expression of hPBP and in Xenopu s oocytes after injection of hPBP. As [S-35]guanosine 5'-3-O-(thio) triphos phate (GTP gammaS) binding to membranes prepared from hPBP-expressing cells was significantly elevate and recombinant hPBP dose-dependently stimulated [S-35] GTP gammaS binding to native membranes, the results presented provi de strong evidence that hPBP-induced effects are G protein-dependent. These data suggest a novel function of hPBP in regulating G protein and G protei n-coupled receptor signaling in vivo.