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.
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Langhans-Rajasekaran SA, Wan Y, Huang XY.; ''Activation of Tsk and Btk tyrosine kinases by G protein beta gamma subunits.''; PubMedEurope PMCScholia
Oude Weernink PA, López de Jesús M, Schmidt M.; ''Phospholipase D signaling: orchestration by PIP2 and small GTPases.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Hanna S, El-Sibai M.; ''Signaling networks of Rho GTPases in cell motility.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Lowry WE, Huang XY.; ''G Protein beta gamma subunits act on the catalytic domain to stimulate Bruton's agammaglobulinemia tyrosine kinase.''; PubMedEurope PMCScholia
Banno Y, Yada Y, Nozawa Y.; ''Purification and characterization of membrane-bound phospholipase C specific for phosphoinositides from human platelets.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Scheid MP, Marignani PA, Woodgett JR.; ''Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B.''; PubMedEurope PMCScholia
Dupré DJ, Robitaille M, Rebois RV, Hébert TE.; ''The role of Gbetagamma subunits in the organization, assembly, and function of GPCR signaling complexes.''; PubMedEurope PMCScholia
Rebecchi MJ, Pentyala SN.; ''Structure, function, and control of phosphoinositide-specific phospholipase C.''; PubMedEurope PMCScholia
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.
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).
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.
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.
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.
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.
Try the New WikiPathways
View approved pathways at the new wikipathways.org.Quality Tags
Ontology Terms
Bibliography
History
External references
DataNodes
beta-gamma:PI3K
gammabeta-gamma:PLC beta
1/2/3Annotated Interactions
beta-gamma:PI3K
gammabeta-gamma:PI3K
gammabeta-gamma:PLC beta
1/2/3beta-gamma:PLC beta
1/2/3