Liganded Gs-activating GPCR acts as a GEF for Gs

Stable Identifier
R-HSA-379044
Type
Reaction [transition]
Species
Homo sapiens
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The liganded receptor undergoes a conformational change, generating a signal that is propagated in a manner that is not completely understood to the the G-protein. This stimulates the exchange of GDP for GTP in the G-protein alpha subunit, activating the G-protein. This event is negatively regulated by some Activators of G protein signaling (AGS) proteins, a class of proteins identified in yeast functional screens for proteins able to activate G protein signaling in the absence of a G protein–coupled receptor (GPCR) (Cismowski et al. 1999, Takesono et al. 1999). AGS proteins contain G protein regulatory (GPR) motifs (also referred to as the GoLoco motif) that bind and stabilize the Galpha subunit in its GDP-bound conformation (Mochizuki et al. 1996, Peterson et al. 2000, Cao et al. 2004, Blumer & Lanier 2014). Some RGS proteins similarly bind to Galpha preventing the exchange of GDP for GTP (Soundararajan et al. 2008).

Literature References
PubMed ID Title Journal Year
12106601 Similarities and differences in the coupling of human beta1- and beta2-adrenoceptors to Gs(alpha) splice variants

Wenzel-Seifert, K, Liu, HY, Seifert, R

Biochem Pharmacol 2002
9651336 Stimulation of type 1 and type 8 Ca2+/calmodulin-sensitive adenylyl cyclases by the Gs-coupled 5-hydroxytryptamine subtype 5-HT7A receptor

Baker, LP, Nielsen, MD, Impey, S, Metcalf, MA, Poser, SW, Chan, G, Obrietan, K, Hamblin, MW, Storm, DR

J Biol Chem 1998
3127824 Isolation and characterization of the human Gs alpha gene

Kozasa, T, Itoh, H, Tsukamoto, T, Kaziro, Y

Proc Natl Acad Sci U S A 1988
12860470 Characterization of the 5-HT6 receptor coupled to Ca2+ signaling using an enabling chimeric G-protein

Zhang, JY, Nawoschik, S, Kowal, D, Smith, D, Spangler, T, Ochalski, R, Schechter, L, Dunlop, J

Eur J Pharmacol 2003
2553705 Multiple signaling pathways of histamine H2 receptors. Identification of an H2 receptor-dependent Ca2+ mobilization pathway in human HL-60 promyelocytic leukemia cells

Mitsuhashi, M, Mitsuhashi, T, Payan, DG

J Biol Chem 1989
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Catalyst Activity
Title
guanyl-nucleotide exchange factor activity of Ligand:GPCR complexes that activate Gs:Heterotrimeric G-protein Gs (inactive) [plasma membrane]
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Orthologous Events
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