Cellular signaling mediated by heterotrimeric G-proteins,comprised of Gα,Gβ,and Gγsubunits,is a major theme in eukaryotic signal transduction pathways(Oldham and Hamm,2008;Pandey,2019).According to the conventional...Cellular signaling mediated by heterotrimeric G-proteins,comprised of Gα,Gβ,and Gγsubunits,is a major theme in eukaryotic signal transduction pathways(Oldham and Hamm,2008;Pandey,2019).According to the conventional paradigm,the guanine nucleotide(GTP or GDP)-bound status of the Gαprotein determines the active versus inactive state of G-protein signaling:the complex stays in an inactive,heterotrimeric form when the Gαis GDP bound.Signal perception or ligand binding to a G-protein-coupled receptor(GPCR)causes an exchange of GDP for GTP on its cognate Gαsubunit;the GPCR thus acts as a guanine-nucleotide exchange factor(GEF).Upon GTP binding,the Gαdissociates from the Gβγsubunits,and both of these entities can interact with downstream effectors to relay information.The Gαprotein has an inherent GTPase activity,which hydrolyzes the bound GTP,and the protein returns to its GDP-bound form,in complex with Gβγ.Therefore,the GEF activity of GPCRs dictates the active(GTP-bound)versus inactive(GDP-bound)stages of G-protein signaling(Oldham and Hamm,2008;Pandey,2019).展开更多
基金supported by National Science Foundation grants(MCB-2207012 and IOS-2421468)to S.P.
文摘Cellular signaling mediated by heterotrimeric G-proteins,comprised of Gα,Gβ,and Gγsubunits,is a major theme in eukaryotic signal transduction pathways(Oldham and Hamm,2008;Pandey,2019).According to the conventional paradigm,the guanine nucleotide(GTP or GDP)-bound status of the Gαprotein determines the active versus inactive state of G-protein signaling:the complex stays in an inactive,heterotrimeric form when the Gαis GDP bound.Signal perception or ligand binding to a G-protein-coupled receptor(GPCR)causes an exchange of GDP for GTP on its cognate Gαsubunit;the GPCR thus acts as a guanine-nucleotide exchange factor(GEF).Upon GTP binding,the Gαdissociates from the Gβγsubunits,and both of these entities can interact with downstream effectors to relay information.The Gαprotein has an inherent GTPase activity,which hydrolyzes the bound GTP,and the protein returns to its GDP-bound form,in complex with Gβγ.Therefore,the GEF activity of GPCRs dictates the active(GTP-bound)versus inactive(GDP-bound)stages of G-protein signaling(Oldham and Hamm,2008;Pandey,2019).
