G alpha (z) signaling events (Homo sapiens)

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10, 12125, 113, 145, 118, 9, 158, 9, 158, 9, 1547, 1226, 185, 1116cytosolADRA2A PRKCD G alpha(s):GTP:AdenylatecyclaseGNB4 GNAI3 GNB2 GTPGNG5 ADRA2B Mg2+ GNG3 ADCY1 GDP GNAZ GNG3 GNG4 GNB4 GNB4 PRKCQ GNAZ GTP ADRA2C GNG12 ADCY9 GNGT2 p(S27)-G-alpha(z):GTP:PKCGNG3 ADRA2C ADCY6 Activated conventional protein kinase C GTP RGS proteins activefor G alpha (z)GNG8 GNAZ GNG13 ADCY1 ADCY2 RGSL1 GTP ADRA2A RGS20 GNB2 GNG2 PiADRA2B GNB3 GNAS2 GTP ADCY8 GNG4 GNG5 GNB2 GNB1 GNG2 GNB3 GNB2 ADRA2A G-protein alpha(z):GTPGNG5 GNGT1 Activated conventional protein kinase C GNG8 PRKCQ GNB5 GNB4 RGS16 GNAZ GNG11 ADCY7 GNG7 GNG13 ADCY3 RGS20 ADCY6 ADCY9 Mg2+ GNG10 ADCY7 ADCY3 RGS16,17,20ADRA2A,B,C:ADR,NAdMg2+ GNAT3 PRKCE GNB5 GNG8 ATPADCY6 ADCY4 GNG8 GTP GNGT2 RGS16 GNG13 Adenylate cyclase(Mg2+ cofactor)RGS20 GNG12 GNG12 ADCY9 ADCY1 p(S27)-G proteinalpha (z):GTPDAG GTP Activated conventional protein kinase C RGS4 RGS17 PRKCE GNG7 GNAS1 NAd GNAZ GNB1 G alpha(z):GDP:RGS16,17,20GNG11 ADPp-S27-GNAZ ADR ADCY5 ADRA2A,B,Cp-S27-GNAZ ADCY2 Ligand:GPCRcomplexes thatactivateGz:HeterotrimericG-protein Gz(inactive)NAd GDP GNAZ G-protein alpha(i):GTP:AdenylatecyclaseGNG12 G-protein beta:gammasignallingMg2+ GTP PRKCE GDP ADRA2C GNG3 ADR ADCY7 NAd GNAZ GNG4 ADCY7 ATPPRKCH GNG7 PRKCH GTP GNG10 GDPcAMPADCY4 GNG5 PRKCD GNB3 PRKCQ ADCY2 GNGT2 GNG7 ADCY2 ADR, NAdRGS16 Protein kinase Cconventional andnovel isoformsADCY4 GNG2 RGS19 GNAZ ADCY5 ADRA2C GNB5 GNGT1 DAG GTP GDP DAG G-alpha(z):GTP:PKCGNAI1 G-protein alpha(z):GTP:AdenylatecyclaseADRA2A ADCY6 ADCY5 GNG2 GNAZ GNB1 GNB1 ADCY8 GNGT1 GNGT1 ADCY3 GNB5 GNG10 GNG4 G-protein alpha(z):GDPGNG10 GNG11 ADRA2B RGS20 ADCY8 ADRA2B PRKCH PPiRGS17 RGS17 RGS17 GNAI2 ADR ADCY8 HeterotrimericG-protein Gz(inactive)NAd G alpha(z):GTP:RGS16,17,20ADCY5 GNB3 G-protein beta-gammacomplexADRA2A-C:Catecholamine:Heterotrimeric G-protein Gz (active)ADCY1 ADR PRKCD GNG11 ADCY4 ADCY9 GNGT2 ADCY3 GNG13 17, 19113


Description

The heterotrimeric G protein G alpha (z), is a member of the G (i) family. Unlike other G alpha (i) 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 (Wong Y H et al. 1992). G alpha (z) interacts with the Rap1 GTPase activating protein (Rap1GAP) to attenuate Rap1 signaling. Like all G-proteins G alpha (z) has an intrinsic GTPase activity, but this activity tends to be lower for the pertussis toxin insensitive G-proteins, most strikingly so for G alpha (z), whose kcat value for GTP hydrolysis is 200-fold lower than those of G alpha (s) or G alpha (i) (Grazziano et al. 1989). G alpha (z) knockout mice have disrupted platelet aggregation at physiological concentrations of epinephrine and responses to several neuroactive drugs are altered (Yang et al. 2000). Regulator of G-protein Signalling (RGS) proteins can regulate the activity of G alpha (z) (Soundararajan M et al. 2008). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 418597
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: Jupe, Steve

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Bibliography

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  1. Dupré DJ, Robitaille M, Rebois RV, Hébert TE.; ''The role of Gbetagamma subunits in the organization, assembly, and function of GPCR signaling complexes.''; PubMed Europe PMC Scholia
  2. Lambert NA.; ''Dissociation of heterotrimeric g proteins in cells.''; PubMed Europe PMC Scholia
  3. Oldham WM, Hamm HE.; ''Structural basis of function in heterotrimeric G proteins.''; PubMed Europe PMC Scholia
  4. Kleuss C, Raw AS, Lee E, Sprang SR, Gilman AG.; ''Mechanism of GTP hydrolysis by G-protein alpha subunits.''; PubMed Europe PMC Scholia
  5. Lounsbury KM, Casey PJ, Brass LF, Manning DR.; ''Phosphorylation of Gz in human platelets. Selectivity and site of modification.''; PubMed Europe PMC Scholia
  6. Wong YH, Conklin BR, Bourne HR.; ''Gz-mediated hormonal inhibition of cyclic AMP accumulation.''; PubMed Europe PMC Scholia
  7. Yang J, Wu J, Kowalska MA, Dalvi A, Prevost N, O'Brien PJ, Manning D, Poncz M, Lucki I, Blendy JA, Brass LF.; ''Loss of signaling through the G protein, Gz, results in abnormal platelet activation and altered responses to psychoactive drugs.''; PubMed Europe PMC Scholia
  8. Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA, Hutsell SQ, Sundström M, Doyle DA, Siderovski DP.; ''Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits.''; PubMed Europe PMC Scholia
  9. Goto K, Doi M, Wang T, Kunisue S, Murai I, Okamura H.; ''G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in the center of the circadian clock [Review].''; PubMed Europe PMC Scholia
  10. Gagnon AW, Manning DR, Catani L, Gewirtz A, Poncz M, Brass LF.; ''Identification of Gz alpha as a pertussis toxin-insensitive G protein in human platelets and megakaryocytes.''; PubMed Europe PMC Scholia
  11. Fields TA, Casey PJ.; ''Phosphorylation of Gz alpha by protein kinase C blocks interaction with the beta gamma complex.''; PubMed Europe PMC Scholia
  12. Ho MK, Wong YH.; ''G(z) signaling: emerging divergence from G(i) signaling.''; PubMed Europe PMC Scholia
  13. Kach J, Sethakorn N, Dulin NO.; ''A finer tuning of G-protein signaling through regulated control of RGS proteins.''; PubMed Europe PMC Scholia
  14. Siderovski DP, Willard FS.; ''The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits.''; PubMed Europe PMC Scholia
  15. Neubig RR, Siderovski DP.; ''Regulators of G-protein signalling as new central nervous system drug targets.''; PubMed Europe PMC Scholia
  16. SUTHERLAND EW, RALL TW.; ''Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles.''; PubMed Europe PMC Scholia
  17. Mao H, Zhao Q, Daigle M, Ghahremani MH, Chidiac P, Albert PR.; ''RGS17/RGSZ2, a novel regulator of Gi/o, Gz, and Gq signaling.''; PubMed Europe PMC Scholia
  18. Chan JS, Chiu TT, Wong YH.; ''Activation of type II adenylyl cyclase by the cloned mu-opioid receptor: coupling to multiple G proteins.''; PubMed Europe PMC Scholia
  19. Wang J, Ducret A, Tu Y, Kozasa T, Aebersold R, Ross EM.; ''RGSZ1, a Gz-selective RGS protein in brain. Structure, membrane association, regulation by Galphaz phosphorylation, and relationship to a Gz gtpase-activating protein subfamily.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
116405view09:03, 7 May 2021EweitzModified title
114771view16:26, 25 January 2021ReactomeTeamReactome version 75
113215view11:28, 2 November 2020ReactomeTeamReactome version 74
112439view15:38, 9 October 2020ReactomeTeamReactome version 73
101715view14:52, 1 November 2018DeSlOntology Term : 'G protein mediated signaling pathway' added !
101344view11:23, 1 November 2018ReactomeTeamreactome version 66
100882view20:57, 31 October 2018ReactomeTeamreactome version 65
100423view19:31, 31 October 2018ReactomeTeamreactome version 64
100271view16:57, 31 October 2018ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADCY1 ProteinQ08828 (Uniprot-TrEMBL)
ADCY2 ProteinQ08462 (Uniprot-TrEMBL)
ADCY3 ProteinO60266 (Uniprot-TrEMBL)
ADCY4 ProteinQ8NFM4 (Uniprot-TrEMBL)
ADCY5 ProteinO95622 (Uniprot-TrEMBL)
ADCY6 ProteinO43306 (Uniprot-TrEMBL)
ADCY7 ProteinP51828 (Uniprot-TrEMBL)
ADCY8 ProteinP40145 (Uniprot-TrEMBL)
ADCY9 ProteinO60503 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:456216 (ChEBI)
ADR MetaboliteCHEBI:28918 (ChEBI)
ADR, NAdComplexR-ALL-390627 (Reactome)
ADRA2A ProteinP08913 (Uniprot-TrEMBL)
ADRA2A,B,C:ADR,NAdComplexR-HSA-390700 (Reactome)
ADRA2A,B,CComplexR-HSA-390664 (Reactome)
ADRA2A-C:Catecholamine:Heterotrimeric G-protein Gz (active)ComplexR-HSA-751030 (Reactome)
ADRA2B ProteinP18089 (Uniprot-TrEMBL)
ADRA2C ProteinP18825 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:30616 (ChEBI)
Activated conventional protein kinase C R-HSA-139830 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ComplexR-HSA-170665 (Reactome)
DAG MetaboliteCHEBI:17815 (ChEBI)
G alpha

(s):GTP:Adenylate

cyclase
ComplexR-HSA-163622 (Reactome)
G alpha (z):GDP:RGS16,17,20ComplexR-HSA-8982024 (Reactome)
G alpha (z):GTP:RGS16,17,20ComplexR-HSA-8981896 (Reactome)
G-alpha(z):GTP:PKCComplexR-HSA-8982710 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
ComplexR-HSA-396910 (Reactome)
G-protein alpha (z):GDPComplexR-HSA-392006 (Reactome)
G-protein alpha

(z):GTP:Adenylate

cyclase
ComplexR-HSA-392049 (Reactome)
G-protein alpha (z):GTPComplexR-HSA-392003 (Reactome)
G-protein beta-gamma complexComplexR-HSA-167434 (Reactome)
G-protein beta:gamma signallingPathwayR-HSA-397795 (Reactome) The classical role of the G-protein beta/gamma dimer was believed to be the inactivation of the alpha subunit, Gbeta/gamma was viewed as a negative regulator of Galpha signalling. It is now known that Gbeta/gamma subunits can directly modulate many effectors, including some also regulated by G alpha.
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GNAI1 ProteinP63096 (Uniprot-TrEMBL)
GNAI2 ProteinP04899 (Uniprot-TrEMBL)
GNAI3 ProteinP08754 (Uniprot-TrEMBL)
GNAS1 ProteinQ5JWF2 (Uniprot-TrEMBL)
GNAS2 ProteinP63092 (Uniprot-TrEMBL)
GNAT3 ProteinA8MTJ3 (Uniprot-TrEMBL)
GNAZ ProteinP19086 (Uniprot-TrEMBL)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNB4 ProteinQ9HAV0 (Uniprot-TrEMBL)
GNB5 ProteinO14775 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG11 ProteinP61952 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG13 ProteinQ9P2W3 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8 ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
Heterotrimeric

G-protein Gz

(inactive)
ComplexR-HSA-391985 (Reactome)
Ligand:GPCR

complexes that activate Gz:Heterotrimeric G-protein Gz

(inactive)
ComplexR-HSA-749450 (Reactome)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NAd MetaboliteCHEBI:18357 (ChEBI)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKCD ProteinQ05655 (Uniprot-TrEMBL)
PRKCE ProteinQ02156 (Uniprot-TrEMBL)
PRKCH ProteinP24723 (Uniprot-TrEMBL)
PRKCQ ProteinQ04759 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:43474 (ChEBI)
Protein kinase C

conventional and

novel isoforms
ComplexR-HSA-804920 (Reactome)
RGS proteins active for G alpha (z)ComplexR-HSA-921140 (Reactome)
RGS16 ProteinO15492 (Uniprot-TrEMBL)
RGS16,17,20ComplexR-HSA-8981894 (Reactome)
RGS17 ProteinQ9UGC6 (Uniprot-TrEMBL)
RGS19 ProteinP49795 (Uniprot-TrEMBL)
RGS20 ProteinO76081 (Uniprot-TrEMBL)
RGS4 ProteinP49798 (Uniprot-TrEMBL)
RGSL1 ProteinA5PLK6 (Uniprot-TrEMBL)
cAMPMetaboliteCHEBI:17489 (ChEBI)
p(S27)-G protein alpha (z):GTPComplexR-HSA-804940 (Reactome)
p(S27)-G-alpha(z):GTP:PKCComplexR-HSA-8982705 (Reactome)
p-S27-GNAZ ProteinP19086 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-751040 (Reactome)
ADR, NAdArrowR-HSA-751024 (Reactome)
ADRA2A,B,C:ADR,NAdR-HSA-749446 (Reactome)
ADRA2A,B,CArrowR-HSA-751024 (Reactome)
ADRA2A-C:Catecholamine:Heterotrimeric G-protein Gz (active)ArrowR-HSA-749453 (Reactome)
ADRA2A-C:Catecholamine:Heterotrimeric G-protein Gz (active)R-HSA-751024 (Reactome)
ATPR-HSA-392129 (Reactome)
ATPR-HSA-751040 (Reactome)
Adenylate cyclase (Mg2+ cofactor)R-HSA-392064 (Reactome)
G alpha

(s):GTP:Adenylate

cyclase
mim-catalysisR-HSA-392129 (Reactome)
G alpha (z):GDP:RGS16,17,20ArrowR-HSA-8982021 (Reactome)
G alpha (z):GDP:RGS16,17,20R-HSA-8982018 (Reactome)
G alpha (z):GTP:RGS16,17,20ArrowR-HSA-8981892 (Reactome)
G alpha (z):GTP:RGS16,17,20R-HSA-8982021 (Reactome)
G alpha (z):GTP:RGS16,17,20mim-catalysisR-HSA-8982021 (Reactome)
G-alpha(z):GTP:PKCArrowR-HSA-8982703 (Reactome)
G-alpha(z):GTP:PKCR-HSA-751040 (Reactome)
G-alpha(z):GTP:PKCmim-catalysisR-HSA-751040 (Reactome)
G-protein alpha (z):GDPArrowR-HSA-392133 (Reactome)
G-protein alpha (z):GDPArrowR-HSA-8982018 (Reactome)
G-protein alpha (z):GDPR-HSA-750988 (Reactome)
G-protein alpha

(z):GTP:Adenylate

cyclase
ArrowR-HSA-392064 (Reactome)
G-protein alpha

(z):GTP:Adenylate

cyclase
TBarR-HSA-392129 (Reactome)
G-protein alpha (z):GTPArrowR-HSA-751024 (Reactome)
G-protein alpha (z):GTPR-HSA-392064 (Reactome)
G-protein alpha (z):GTPR-HSA-392133 (Reactome)
G-protein alpha (z):GTPR-HSA-8981892 (Reactome)
G-protein alpha (z):GTPR-HSA-8982703 (Reactome)
G-protein alpha (z):GTPmim-catalysisR-HSA-392133 (Reactome)
G-protein beta-gamma complexArrowR-HSA-751024 (Reactome)
G-protein beta-gamma complexR-HSA-750988 (Reactome)
GDPArrowR-HSA-749453 (Reactome)
GTPR-HSA-749453 (Reactome)
Heterotrimeric

G-protein Gz

(inactive)
ArrowR-HSA-750988 (Reactome)
Heterotrimeric

G-protein Gz

(inactive)
R-HSA-749446 (Reactome)
Ligand:GPCR

complexes that activate Gz:Heterotrimeric G-protein Gz

(inactive)
ArrowR-HSA-749446 (Reactome)
Ligand:GPCR

complexes that activate Gz:Heterotrimeric G-protein Gz

(inactive)
R-HSA-749453 (Reactome)
Ligand:GPCR

complexes that activate Gz:Heterotrimeric G-protein Gz

(inactive)
mim-catalysisR-HSA-749453 (Reactome)
PPiArrowR-HSA-392129 (Reactome)
PiArrowR-HSA-8982021 (Reactome)
Protein kinase C

conventional and

novel isoforms
ArrowR-HSA-8982709 (Reactome)
Protein kinase C

conventional and

novel isoforms
R-HSA-8982703 (Reactome)
R-HSA-392064 (Reactome) G-proteins in the Gi class inhibit adenylate cyclase activity, decreasing the production of cAMP from ATP, which has many consequences but classically results in decreased activity of Protein Kinase A (PKA). cAMP also activates the cyclic nucleotide-gated ion channels, a process that is particularly important in olfactory cells. Experimental data for this reaction was obtained in vitro using rat G alpha (i) and dog Adenylate Cyclase.
R-HSA-392129 (Reactome) The activation of adenylyl (adenylate) cyclase (AC) results in the production of adenosine-3',5'-monophosphate i.e. cyclic AMP. Humans have 9 genes encoding membrane-associated AC and one encoding a soluble AC. Two of the classes of heterotrimeric G-proteins are named according to their effect on AC; G(s) stimulates all membrane-bound ACs (the s in G(s) denotes AC stimulatory); the G(i) class inhibits some AC isoforms, particularly 5 and 6. Beta-gamma subunits of heterotrimeric G-proteins can also regulate AC. Ca2+/Calmodulin activates some AC isoforms (1, 8 and 3) but is inhibitory to others (5 and 6).
R-HSA-392133 (Reactome) When a ligand activates a G protein-coupled receptor, it induces a conformational change in the receptor (a change in shape) that allows the receptor to function as a guanine nucleotide exchange factor (GEF), stimulating the exchange of GDP for GTP on the G alpha subunit. In the traditional view of heterotrimeric protein activation, this exchange triggers the dissociation of the now active G alpha subunit from the beta:gamma dimer, initiating downstream signalling events. The G alpha subunit has intrinsic GTPase activity and will eventually hydrolyze the attached GTP to GDP, allowing reassociation with G beta:gamma. Additional GTPase-activating proteins (GAPs) stimulate the GTPase activity of G alpha, leading to more rapid termination of the transduced signal. In some cases the downstream effector may have GAP activity, helping to deactivate the pathway. This is the case for phospholipase C beta, which possesses GAP activity within its C-terminal region (Kleuss et al. 1994).
R-HSA-749446 (Reactome) Gz is predominantly expressed in the nervous system and platelets. Gz interacts with receptors for many neurotransmitters and neuropeptides, including the adenosine A1, alpha2-adrenergic, dopamine D2, 5-HT1A, muscarinic M2, substance P, and all types of opioid receptors. In addition, Gz is capable of transducing signals from receptors such as the C5a and formyl peptide receptors. All these receptors can also signal via Gi. (Ho & Wong 2001).
R-HSA-749453 (Reactome) 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).
R-HSA-750988 (Reactome) The classical model of G-protein signaling suggests that the G-protein dissociates upon GPCR activation. The active G alpha (z) subunit then participates in signaling, until its intrinsic GTPase activity degrades the bound GTP to GDP. The inactive G alpha (z):GDP complex has much higher affinity for the G beta:gamma complex and consequently reassociates.
R-HSA-751024 (Reactome) The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. Activated G alpha (z) and the beta:gamma dimer then participate in separate signaling cascades. Although G protein dissociation has been contested (e.g. Bassi et al. 1996), recent in vivo experiments have demonstrated that dissociation does occur, though possibly not to completion (Lambert 2008).
R-HSA-751040 (Reactome) G alpha z (Lounsbury et al. 1991) and G alpha 12 (Kozasa & Gilman, 1996) are excellent in vitro substrates for all three subtypes of protein kinase C (PKC). Activation of PKC in intact platelets by agents such as thrombin, thromboxane A2 (TXA2) analogues and phorbol esters leads to rapid and near-stoichiometric phosphorylation of G alpha z (Carlson et al. 1989). The primary phosphorylation site is Ser-27 (Lounsbury et al. 1993). This phosphorylation blocks the interaction of G alpha z with Gbeta:gamma suggesting that it is a regulatory mechanism for attenuating signalling by preventing subunit reassociation.
R-HSA-8981892 (Reactome) G Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G proteins). Upon activation, GPCRs can replace the GDP with GTP in the alpha subunit of G proteins. GTP binding modifies the conformation of G alpha proteins and activates them. The Regulator of G protein Signalling (RGS) are GTPase Accelerating Proteins (GAPs) that can directly inhibit the G alpha subunit activity. There are at least 25 different types of RGS proteins known. RGS16, RGS17 and RGS20 can bind and stabilize the transition state of Guanine nucleotide binding protein G(z) subunit alpha (GNAZ) along its path to GTP hydrolysis. Subsequently, this leads to GTP hydrolysis and inactivation of GNAZ, terminating downstream signalling (Neubig & Siderovski 2002, Kach et al. 2012, Goto K et al. 2017). GNAZ inhibits adenylyl cyclase and interacts with Rap1GAP to attenuate Rap1 signaling.
R-HSA-8982018 (Reactome) G Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G proteins). Upon activation, GPCRs can replace the GDP with GTP in the alpha subunit of G proteins. GTP binding modifies the conformation of G alpha proteins and activates them. The Regulator of G protein Signalling (RGS) are GTPase Accelerating Proteins (GAPs) that can directly inhibit the G alpha subunit activity. There are at least 25 different types of RGS proteins known. RGS16, RGS17 and RGS20 can bind and stabilize the transition state of Guanine nucleotide binding protein G(z) subunit alpha (GNAZ). Subsequently, RGS proteins in the complex facilitate the hydrolysis of GNAZ:GTP to GNAZ:GDP. Following this, the complex dissociates releasing inactive GNAZ ((Neubig & Siderovski 2002, Kach et al. 2012, Goto K et al. 2017). GNAZ inhibits adenylyl cyclase and interacts with Rap1GAP to attenuate Rap1 signaling.
R-HSA-8982021 (Reactome) G Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G proteins). Upon activation, GPCRs can replace the GDP with GTP in the alpha subunit of G proteins. GTP binding modifies the conformation of G alpha proteins and activates them. The Regulator of G protein Signalling (RGS) are GTPase Accelerating Proteins (GAPs) that can directly inhibit the G alpha subunit activity. There are at least 25 different types of RGS proteins known. RGS16, RGS17 and RGS20 can bind and stabilize the transition state of Guanine nucleotide binding protein G(z) subunit alpha (GNAZ). Following this, RGS exerts its GAP activity on GNAZ and facilitates the hydrolyses GTP to GDP. This inactivates GNAZ and terminates downstream signalling (Neubig & Siderovski 2002, Kach et al. 2012, Goto K et al. 2017). GNAZ inhibits adenylyl cyclase and interacts with Rap1GAP to attenuate Rap1 signaling.
R-HSA-8982703 (Reactome) G alpha z (Lounsbury et al. 1991) and G alpha 12 (Kozasa & Gilman, 1996) are excellent in vitro substrates for all three subtypes of protein kinase C (PKC). Activation of PKC in intact platelets by agents such as thrombin, thromboxane A2 (TXA2) analogues and phorbol esters leads to rapid and near-stoichiometric phosphorylation of G alpha z (Carlson et al. 1989). PKC can bind to G alpha z and facilitate its phosphorylation at Ser-27 (Lounsbury et al. 1993). This phosphorylation blocks the interaction of G alpha z with Gbeta:gamma suggesting that it is a regulatory mechanism for attenuating signalling by preventing subunit reassociation.
R-HSA-8982709 (Reactome) G alpha z (Lounsbury et al. 1991) and G alpha 12 (Kozasa & Gilman, 1996) are excellent in vitro substrates for all three subtypes of protein kinase C (PKC). Activation of PKC in intact platelets by agents such as thrombin, thromboxane A2 (TXA2) analogues and phorbol esters leads to rapid and near-stoichiometric phosphorylation of G alpha z (Carlson et al. 1989). PKC can bind to G alpha z and facilitate phosphorylation at Ser-27 (Lounsbury et al. 1993). Subsequently, phosphorylated G alpha z dissociates from the complex. This phosphorylation blocks the interaction of G alpha z with Gbeta:gamma suggesting that it is a regulatory mechanism for attenuating signalling by preventing subunit reassociation.
RGS proteins active for G alpha (z)ArrowR-HSA-392133 (Reactome)
RGS16,17,20ArrowR-HSA-8982018 (Reactome)
RGS16,17,20R-HSA-8981892 (Reactome)
TBarR-HSA-392129 (Reactome)
cAMPArrowR-HSA-392129 (Reactome)
p(S27)-G protein alpha (z):GTPArrowR-HSA-8982709 (Reactome)
p(S27)-G-alpha(z):GTP:PKCArrowR-HSA-751040 (Reactome)
p(S27)-G-alpha(z):GTP:PKCR-HSA-8982709 (Reactome)
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