Adenylate cyclase converts ATP to 3',5'-cyclic AMP (cAMP) and pyrophosphate Liganded Gz-activating GPCRs bind inactive heterotrimeric G-protein Gz The Ligand:GPCR:Gz complex dissociates Liganded Gz-activating GPCR acts as a GEF for Gz Gz is a substrate for PKC G alpha (z) inhibits adenylate cyclase Inactive G alpha (z) reassociates with G beta:gamma G alpha (z) auto-inactivates by hydrolysing GTP to GDP PathwayStep5733 PathwayStep5751 PathwayStep5750 PathwayStep5745 PathwayStep5746 PathwayStep5747 PathwayStep5748 PathwayStep5749 G alpha (z) signalling events Authored: Jupe, S, 2009-04-24 08:15:10 Edited: Jupe, S, 2009-09-09 Pubmed10954748 Pubmed11313909 Pubmed1908722 Pubmed2491850 Pubmed9032437 Reactome Database ID Release 43418597 Reactome, http://www.reactome.org ReactomeREACT_19333 Reviewed: Akkerman, JW, 2009-06-03 The heterotrimeric G protein Gz, is a member of the Gi family. Unlike other Gi family members it lacks an ADP ribosylation site cysteine four residues from the carboxyl terminus and is thus pertussis toxin-insensitive. It inhibits adenylyl cyclase types I, V and VI. G alpha (z) interacts with the Rap1 GTPase activating protein (Rap1GAP) to attenuate Rap1 signaling. Like all G-proteins Gz has an intrinsic GTPase activity, but this activity tends to be lower for the pertussis toxin insensitive G-proteins, most strikingly so for Gz, whose kcat value for GTP hydrolysis is 200-fold lower than those of Gs or Gi (Grazziano et al. 1989). Gz knockout mice have disrupted platelet aggregation at physiological concentrations of epinephrine and responses to several neuroactive drugs are altered (Yang et al. 2000).