G-protein beta:gamma signaling (Homo sapiens)

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7462, 3, 101, 589cytosolPIK3R1 GNGT2 PLCB1 GNG2 GNGT2 p-Y-GAB2 AKT3 DAGG-proteinbeta-gamma:PLC beta1/2/3GNGT1 PDPK1 PI(3,4,5)P3High affinity binding complex dimers of cytokine receptors using Bc, inactive JAK2, p(Y593,628)- Bc:p(427,349,350)-SHC1:GRB2:p(Y)-GAB2:p85-containing Class 1A PI3Ks GNGT1 RHOAPI(3,4,5)P3 GNG7 GNGT1 GNB1 GNG13 GNG3 GNB3 PDPK1GNG5 GNB1 PLCB3 PLCB2 GNB2 PLCB1 G-protein beta-gammacomplexPIP3:RhoAG-proteinbeta-gamma:PI3KgammaAKT1 IL2RA GNG10 GNG11 PIK3R2 GNB1 PLCB2 GNG4 RHOA I(1,4,5)P3GNB2 GNB4 AKTGNG12 GNG5 GNG8 PIK3CA GNG8 GNG3 PIK3CB GNG11 PIK3CG GNB2 AKT2 PI(4,5)P2GNG7 IL2 PLC-beta 1/2/3p-Y-JAK1 GNG5 GNG4 GNG2 ADPPIK3R5 GNGT2 PIK3CG GNB5 GNG13 JAK3 GNG11 AKT1 InterleukinreceptorcomplexeswithactivatedShc:GRB2:p-GAB2:p85-containing Class 1 PI3KsGNG2 GNG4 GNG7 p-Y364,Y418,Y536-IL2RB PIK3R3 GNB4 GRB2-1 AKT2 PIK3CD PLCB3 GNG3 GNG10 GNG13 GNG10 PIK3R6 IL2RG AKT3 GNG12 GNB5 GNB3 PI3K gammaGNG12 ATPPDK1:AKT:PIP3GNG8 PIK3R6 PI(3,4,5)P3 GNB4 PIK3R5 p-Y-SHC1 GNB3 GNB5


Description

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. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 397795
Reactome-version 
Reactome version: 64
Reactome Author 
Reactome Author: Jupe, Steve

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Ontology Terms

 

Bibliography

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  1. Brock C, Schaefer M, Reusch HP, Czupalla C, Michalke M, Spicher K, Schultz G, Nürnberg B.; ''Roles of G beta gamma in membrane recruitment and activation of p110 gamma/p101 phosphoinositide 3-kinase gamma.''; PubMed Europe PMC Scholia
  2. Laederach A, Cradic KW, Brazin KN, Zamoon J, Fulton DB, Huang XY, Andreotti AH.; ''Competing modes of self-association in the regulatory domains of Bruton's tyrosine kinase: intramolecular contact versus asymmetric homodimerization.''; PubMed Europe PMC Scholia
  3. Langhans-Rajasekaran SA, Wan Y, Huang XY.; ''Activation of Tsk and Btk tyrosine kinases by G protein beta gamma subunits.''; PubMed Europe PMC Scholia
  4. Oude Weernink PA, López de Jesús M, Schmidt M.; ''Phospholipase D signaling: orchestration by PIP2 and small GTPases.''; PubMed Europe PMC Scholia
  5. Stoyanov B, Volinia S, Hanck T, Rubio I, Loubtchenkov M, Malek D, Stoyanova S, Vanhaesebroeck B, Dhand R, Nürnberg B.; ''Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase.''; PubMed Europe PMC Scholia
  6. Hanna S, El-Sibai M.; ''Signaling networks of Rho GTPases in cell motility.''; PubMed Europe PMC Scholia
  7. Chong LD, Traynor-Kaplan A, Bokoch GM, Schwartz MA.; ''The small GTP-binding protein Rho regulates a phosphatidylinositol 4-phosphate 5-kinase in mammalian cells.''; PubMed Europe PMC Scholia
  8. Lowry WE, Huang XY.; ''G Protein beta gamma subunits act on the catalytic domain to stimulate Bruton's agammaglobulinemia tyrosine kinase.''; PubMed Europe PMC Scholia
  9. Banno Y, Yada Y, Nozawa Y.; ''Purification and characterization of membrane-bound phospholipase C specific for phosphoinositides from human platelets.''; PubMed Europe PMC Scholia
  10. Li Z, Hannigan M, Mo Z, Liu B, Lu W, Wu Y, Smrcka AV, Wu G, Li L, Liu M, Huang CK, Wu D.; ''Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42.''; PubMed Europe PMC Scholia
  11. Bonacci TM, Ghosh M, Malik S, Smrcka AV.; ''Regulatory interactions between the amino terminus of G-protein betagamma subunits and the catalytic domain of phospholipase Cbeta2.''; PubMed Europe PMC Scholia
  12. Scheid MP, Marignani PA, Woodgett JR.; ''Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B.''; PubMed Europe PMC Scholia
  13. 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
  14. Rebecchi MJ, Pentyala SN.; ''Structure, function, and control of phosphoinositide-specific phospholipase C.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
116432view09:28, 7 May 2021EweitzModified title
115003view16:53, 25 January 2021ReactomeTeamReactome version 75
113447view11:52, 2 November 2020ReactomeTeamReactome version 74
112647view16:03, 9 October 2020ReactomeTeamReactome version 73
101707view14:49, 1 November 2018DeSlOntology Term : 'G protein mediated signaling pathway' added !
101562view11:43, 1 November 2018ReactomeTeamreactome version 66
101098view21:26, 31 October 2018ReactomeTeamreactome version 65
100627view20:00, 31 October 2018ReactomeTeamreactome version 64
100277view16:57, 31 October 2018ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
AKT1 ProteinP31749 (Uniprot-TrEMBL)
AKT2 ProteinP31751 (Uniprot-TrEMBL)
AKT3 ProteinQ9Y243 (Uniprot-TrEMBL)
AKTComplexR-HSA-202088 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
ATPMetaboliteCHEBI:15422 (ChEBI)
DAGMetaboliteCHEBI:17815 (ChEBI)
G-protein

beta-gamma:PI3K

gamma
ComplexR-HSA-392293 (Reactome)
G-protein

beta-gamma:PLC beta

1/2/3
ComplexR-HSA-398037 (Reactome)
G-protein beta-gamma complexComplexR-HSA-167434 (Reactome)
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)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
High affinity binding complex dimers of cytokine receptors using Bc, inactive JAK2, p(Y593,628)- Bc:p(427,349,350)-SHC1:GRB2:p(Y)-GAB2:p85-containing Class 1A PI3Ks R-HSA-926776 (Reactome)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
IL2 ProteinP60568 (Uniprot-TrEMBL)
IL2RA ProteinP01589 (Uniprot-TrEMBL)
IL2RG ProteinP31785 (Uniprot-TrEMBL)
Interleukin

receptor complexes with activated

Shc:GRB2:p-GAB2:p85-containing Class 1 PI3Ks
ComplexR-HSA-912535 (Reactome)
JAK3 ProteinP52333 (Uniprot-TrEMBL)
PDK1:AKT:PIP3ComplexR-HSA-198360 (Reactome)
PDPK1 ProteinO15530 (Uniprot-TrEMBL)
PDPK1ProteinO15530 (Uniprot-TrEMBL)
PI(3,4,5)P3 MetaboliteCHEBI:16618 (ChEBI)
PI(3,4,5)P3MetaboliteCHEBI:16618 (ChEBI)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PI3K gammaComplexR-HSA-392291 (Reactome)
PIK3CA ProteinP42336 (Uniprot-TrEMBL)
PIK3CB ProteinP42338 (Uniprot-TrEMBL)
PIK3CD ProteinO00329 (Uniprot-TrEMBL)
PIK3CG ProteinP48736 (Uniprot-TrEMBL)
PIK3R1 ProteinP27986 (Uniprot-TrEMBL)
PIK3R2 ProteinO00459 (Uniprot-TrEMBL)
PIK3R3 ProteinQ92569 (Uniprot-TrEMBL)
PIK3R5 ProteinQ8WYR1 (Uniprot-TrEMBL)
PIK3R6 ProteinQ5UE93 (Uniprot-TrEMBL)
PIP3:RhoAComplexR-HSA-202676 (Reactome)
PLC-beta 1/2/3ComplexR-HSA-425749 (Reactome)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3 ProteinQ01970 (Uniprot-TrEMBL)
RHOA ProteinP61586 (Uniprot-TrEMBL)
RHOAProteinP61586 (Uniprot-TrEMBL)
p-Y-GAB2 ProteinQ9UQC2 (Uniprot-TrEMBL)
p-Y-JAK1 ProteinP23458 (Uniprot-TrEMBL)
p-Y-SHC1 ProteinP29353 (Uniprot-TrEMBL)
p-Y364,Y418,Y536-IL2RB ProteinP14784 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-392300 (Reactome)
AKTR-HSA-198284 (Reactome)
ATPR-HSA-392300 (Reactome)
DAGArrowR-HSA-398193 (Reactome)
G-protein

beta-gamma:PI3K

gamma
ArrowR-HSA-392295 (Reactome)
G-protein

beta-gamma:PI3K

gamma
mim-catalysisR-HSA-392300 (Reactome)
G-protein

beta-gamma:PLC beta

1/2/3
ArrowR-HSA-398040 (Reactome)
G-protein

beta-gamma:PLC beta

1/2/3
mim-catalysisR-HSA-398193 (Reactome)
G-protein beta-gamma complexR-HSA-392295 (Reactome)
G-protein beta-gamma complexR-HSA-398040 (Reactome)
I(1,4,5)P3ArrowR-HSA-398193 (Reactome)
Interleukin

receptor complexes with activated

Shc:GRB2:p-GAB2:p85-containing Class 1 PI3Ks
ArrowR-HSA-198284 (Reactome)
PDK1:AKT:PIP3ArrowR-HSA-198284 (Reactome)
PDPK1R-HSA-198284 (Reactome)
PI(3,4,5)P3ArrowR-HSA-392300 (Reactome)
PI(3,4,5)P3R-HSA-198284 (Reactome)
PI(3,4,5)P3R-HSA-202692 (Reactome)
PI(4,5)P2R-HSA-392300 (Reactome)
PI(4,5)P2R-HSA-398193 (Reactome)
PI3K gammaR-HSA-392295 (Reactome)
PIP3:RhoAArrowR-HSA-202692 (Reactome)
PLC-beta 1/2/3R-HSA-398040 (Reactome)
R-HSA-198284 (Reactome) Phosphatidylinositides generated by PI3K recruit phosphatidylinositide-dependent protein kinase 1 (PDK1) and AKT (also known as protein kinase B) to the membrane, through their PH (pleckstrin-homology) domains. The binding of PIP3 to the PH domain of AKT is the rate-limiting step in AKT activation. In mammals there are three AKT isoforms (AKT1-3) encoded by three separate genes. The three isoforms share a high degree of amino acid identity and have indistinguishable substrate specificity in vitro. However, isoform-preferred substrates in vivo cannot be ruled out. The relative expression of the three isoforms differs in different mammalian tissues: AKT1 is the predominant isoform in the majority of tissues, AKT2 is the predominant isoform in insulin-responsive tissues, and AKT3 is the predominant isoform in brain and testes. All 3 isoforms are expressed in human and mouse platelets (Yin et al. 2008; O'Brien et al. 2008). Note: all data in the pathway refer to AKT1, which is the most studied.
R-HSA-202692 (Reactome) Several guanine exchange factors (GEFs) for the Rho family of GTPases contain PH domains that bind to PIP3. RhoA protein activation is a mechanism whereby PI3K acts independently of AKT (Chong et al. 1994, Oude Weernink et al. 1997).
R-HSA-392295 (Reactome) G beta:gamma recruits PI3K gamma from the cytosol to the plasma membrane by interacting with the p101 regulatory subunit. G beta:gamma activates PI3Kgamma via interactions with the catalytic p110 subunit.
R-HSA-392300 (Reactome) Biochemical and cellular studies have shown that the p101/p110 form of PI3K gamma is substantially activated by G beta:gamma in a manner that is dependent on p101.
R-HSA-398040 (Reactome) G beta:gamma engages the PH domain of Phospholipase C beta, stimulating phospholipase activity, resulting in increased PIP2 hydrolysis.
R-HSA-398193 (Reactome) Phospholipase C (PLC) isozymes are a group of related proteins that cleave the polar head group from inositol phospholipids, typically in response to signals from cell surface receptors. They hydrolyze the highly phosphorylated lipid phosphatidylinositol 4,5-bisphosphate (PIP2) generating two products: inositol 1,4,5-trisphosphate (IP3), a universal calcium-mobilizing second messenger, and diacylglycerol (DAG), an activator of protein kinase C. PLC-beta isoforms are regulated by heterotrimeric GTP-binding proteins. PLC-beta 1 and 3 are widely expressed, with the highest concentrations found in (differing) specific regions of the brain. PLC-beta 2 is expressed at highest levels in cells of hematopoeitic origin; it is involved in leukocyte signaling and host defense. PLC-beta 4 is highly concentrated in cerebellar Purkinje and granule cells, the median geniculate body, whose axons terminate in the auditory cortex, and the lateral geniculate nucleus, where most retinal axons terminate in a visuotopic representation of each half of the visual field.
RHOAR-HSA-202692 (Reactome)
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