G-protein beta:gamma signaling (Homo sapiens)

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109999115, 12, 131, 3, 4712, 132612, 138, 1499cytosolPIP3:ActiveBTK:G-proteinbeta-gamma complexGNB2 GNG5 GNB4 PDK1:AKT:PIP3GNB5 GNG7 GNGT2 GNG12 GNG2 PLCB3 GNB2 AKT2 GNB3 GNG3 GNG8 GNGT1 GNG4 GNGT1 GNG5 GNG12 GNG12 GNGT1 ATPGNB4 GNB1 GNG11 GNGT2 GNG12 PAK1 Active PAK1GNG13 GNG5 GNB3 GNG5 GNB1 GNB4 PIK3R6 GNG3 GNB4 GNB5 GNB2 PI3K gammaGNG5 GNG11 CDC42 GNB2 GNG7 PLCB3 GNB4 GNB1 GNB2 GNB5 GNG4 GNG3 PAK1:ARHGEF6AKT2 GNGT1 GTP GNB5 GNB1 GNG11 AKT3 GNB3 GNG2 G-proteinbeta-gammacomplex:PAK1:ARHGEF6GNG8 GNGT2 GNB2 PIK3R5 G-proteinbeta-gammacomplex:PAK1:ARHGEF6:Active CDC42GNG13 PLCB1 RHOAGNG11 GNGT1 GNG7 CDC42PIK3CG GNG7 PI(3,4,5)P3 GNG11 GNG3 AKT3 GNGT2 ARHGEF6PIK3R6 GNB5 PI(4,5)P2GNG4 Active BTKG-protein beta-gammacomplex:ActivePAK1:ARHGEF6:ActiveCDC42PI(3,4,5)P3 GNG8 AKT1 GNG10 GNB1 GNG8 GNG5 GNG3 PDPK1 BTK GNG10 RHOA GNG10 GNB3 GNB1 PLC-beta 1/2/3GNG4 GTP PIK3CG GNG10 PLCB2 GNG3 GNG13 GNB5 GNB2 PI(3,4,5)P3 GNG2 G-protein beta-gammacomplexGNG7 GNG7 GNG5 PI(3,4,5)P3GNG4 GNG11 G-proteinbeta-gammacomplex:PAK1:ARHGEF6:CDC42GNG5 GNG10 PIP3:RhoAAKT1 GNGT2 GNG7 GNG10 GNB2 GNG11 GNG8 GNG3 GNB2 GNG3 I(1,4,5)P3ARHGEF6 G-proteinbeta-gamma:PLC beta1/2/3GNG13 PAK1 Active PAK1 PAK1 AKTARHGEF6 GNG12 GNGT2 GNG13 PI(3,4,5)P3GNGT1 GNB4 GNG10 GNG2 DAGGNG12 PIP3:BTK:G-proteinbeta-gamma complexPIK3R5 GNB4 GNG8 GNB3 GNGT1 GNG3 GNB3 GNG11 GNB1 GNGT2 GNG7 GNB3 GNB5 Active BTK GNB4 GNG12 GNG4 PLCB2 GNGT1 GNG10 GNG2 GNB1 CDC42 GNG5 G-proteinbeta-gamma:PI3KgammaBTKGNB1 GNG13 GNG8 ARHGEF6 GNGT2 GNG10 GNG2 PLCB1 GNB5 GNG4 PI(3,4,5)P3 GNG13 GNG4 ARHGEF6 GTP GNG2 GNG13 GNG12 GNG2 CDC42 PAK1 PDPK1GNG2 GNG8 GNB5 PAK1GNB3 CDC42:GTPGNG13 GNG12 GNG8 GNGT2 ADPGNB4 GNGT1 GNG11 GNG7 GNB3 GNG4 ARHGEF6 CDC42


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: 73
Reactome Author 
Reactome Author: Jupe, Steve

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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:456216 (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.
ARHGEF6 ProteinQ15052 (Uniprot-TrEMBL)
ARHGEF6ProteinQ15052 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:30616 (ChEBI)
Active BTK ProteinQ06187 (Uniprot-TrEMBL)
Active BTKProteinQ06187 (Uniprot-TrEMBL)
Active PAK1 ProteinQ13153 (Uniprot-TrEMBL)
Active PAK1ProteinQ13153 (Uniprot-TrEMBL)
BTK ProteinQ06187 (Uniprot-TrEMBL)
BTKProteinQ06187 (Uniprot-TrEMBL)
CDC42 ProteinP60953 (Uniprot-TrEMBL)
CDC42:GTPComplexR-HSA-182921 (Reactome)
CDC42ProteinP60953 (Uniprot-TrEMBL)
DAGMetaboliteCHEBI:17815 (ChEBI)
G-protein

beta-gamma

complex:PAK1:ARHGEF6:Active CDC42
ComplexR-HSA-8964618 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6:CDC42
ComplexR-HSA-8964627 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6
ComplexR-HSA-8964608 (Reactome)
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

complex:Active PAK1:ARHGEF6:Active

CDC42
ComplexR-HSA-9014577 (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)
GTP MetaboliteCHEBI:15996 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
PAK1 ProteinQ13153 (Uniprot-TrEMBL)
PAK1:ARHGEF6ComplexR-HSA-8964628 (Reactome)
PAK1ProteinQ13153 (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)
PIK3CG ProteinP48736 (Uniprot-TrEMBL)
PIK3R5 ProteinQ8WYR1 (Uniprot-TrEMBL)
PIK3R6 ProteinQ5UE93 (Uniprot-TrEMBL)
PIP3:Active

BTK:G-protein

beta-gamma complex
ComplexR-HSA-8964267 (Reactome)
PIP3:BTK:G-protein beta-gamma complexComplexR-HSA-8964249 (Reactome)
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)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-392300 (Reactome)
AKTR-HSA-9603279 (Reactome)
ARHGEF6ArrowR-HSA-8964599 (Reactome)
ARHGEF6R-HSA-8964619 (Reactome)
ATPR-HSA-392300 (Reactome)
Active BTKArrowR-HSA-8964317 (Reactome)
Active PAK1ArrowR-HSA-8964599 (Reactome)
BTKR-HSA-8964241 (Reactome)
CDC42:GTPArrowR-HSA-8964599 (Reactome)
CDC42R-HSA-8964634 (Reactome)
DAGArrowR-HSA-398193 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6:Active CDC42
ArrowR-HSA-8964604 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6:Active CDC42
R-HSA-8964614 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6:CDC42
ArrowR-HSA-8964634 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6:CDC42
R-HSA-8964604 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6:CDC42
mim-catalysisR-HSA-8964604 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6
ArrowR-HSA-8964605 (Reactome)
G-protein

beta-gamma

complex:PAK1:ARHGEF6
R-HSA-8964634 (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

complex:Active PAK1:ARHGEF6:Active

CDC42
ArrowR-HSA-8964614 (Reactome)
G-protein beta-gamma

complex:Active PAK1:ARHGEF6:Active

CDC42
R-HSA-8964599 (Reactome)
G-protein beta-gamma complexArrowR-HSA-8964317 (Reactome)
G-protein beta-gamma complexArrowR-HSA-8964599 (Reactome)
G-protein beta-gamma complexR-HSA-392295 (Reactome)
G-protein beta-gamma complexR-HSA-398040 (Reactome)
G-protein beta-gamma complexR-HSA-8964241 (Reactome)
G-protein beta-gamma complexR-HSA-8964605 (Reactome)
I(1,4,5)P3ArrowR-HSA-398193 (Reactome)
PAK1:ARHGEF6ArrowR-HSA-8964619 (Reactome)
PAK1:ARHGEF6R-HSA-8964605 (Reactome)
PAK1R-HSA-8964619 (Reactome)
PDK1:AKT:PIP3ArrowR-HSA-9603279 (Reactome)
PDPK1R-HSA-9603279 (Reactome)
PI(3,4,5)P3ArrowR-HSA-392300 (Reactome)
PI(3,4,5)P3ArrowR-HSA-8964317 (Reactome)
PI(3,4,5)P3R-HSA-202692 (Reactome)
PI(3,4,5)P3R-HSA-8964241 (Reactome)
PI(3,4,5)P3R-HSA-9603279 (Reactome)
PI(4,5)P2R-HSA-392300 (Reactome)
PI(4,5)P2R-HSA-398193 (Reactome)
PI3K gammaR-HSA-392295 (Reactome)
PIP3:Active

BTK:G-protein

beta-gamma complex
ArrowR-HSA-8964271 (Reactome)
PIP3:Active

BTK:G-protein

beta-gamma complex
R-HSA-8964317 (Reactome)
PIP3:BTK:G-protein beta-gamma complexArrowR-HSA-8964241 (Reactome)
PIP3:BTK:G-protein beta-gamma complexR-HSA-8964271 (Reactome)
PIP3:RhoAArrowR-HSA-202692 (Reactome)
PLC-beta 1/2/3R-HSA-398040 (Reactome)
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.
R-HSA-8964241 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. G-protein beta-gamma complex, along with phosphatidylinositol 3,4,5-trisphosphate (PIP3), recruits the non-receptor Tyrosine-protein kinase BTK to the cell membrane. This recruitment involves binding of the G-protein beta-gamma complex to the pleckstrin homology/Tec-homology module of Btk. Here, BTK is activated and subsequently released to the cytoplasm. Physiologically, BTK plays a key role in B lymphocyte development, differentiation and signalling.
R-HSA-8964271 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. G-protein beta-gamma complex, along with phosphatidylinositol 3,4,5-trisphosphate (PIP3), recruits the non-receptor Tyrosine-protein kinase BTK to the cell membrane. In the membrane, the G-protein beta-gamma complex binds to the catalytic domain of BTK and activates it. Active BTK is then released to the cytoplasm. Physiologically, BTK plays a key role in B lymphocyte development, differentiation and signalling.
R-HSA-8964317 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. G-protein beta-gamma complex, along with phosphatidylinositol 3,4,5-trisphosphate (PIP3), recruits the non-receptor Tyrosine-protein kinase BTK to the cell membrane. Here, the G-protein beta-gamma complex activates BTK. Once active, BTK dissociates from PIP3 and G-protein beta-gamma complex and is released to the cytoplasm to phosphorylate downstream substrates. Physiologically, BTK plays a key role in B lymphocyte development, differentiation and signalling.
R-HSA-8964599 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. Serine/threonine-protein kinase PAK 1 binds with Rho guanine nucleotide exchange factor 6 (ARHGEF6, PIX-Alpha) in the cytosol and is subsequently translocated by the G-protein beta-gamma complex to the plasma membrane. Here, ARHGEF6 activates Cell division control protein 42 homolog (CDC42) by acting as a GEF. Once active, CDC42 can facilitate the activation of PAK1. At this stage the whole complex dissociates to release the active CDC42 and active PAK1. CDC42 is known to be involved in epithelial cell polarization processes. PAK1 plays an important role in cytoskeleton dynamics and cell adhesion.
R-HSA-8964604 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. Serine/threonine-protein kinase PAK 1 binds with Rho guanine nucleotide exchange factor 6 (ARHGEF6, PIX-Alpha) in the cytosol and is subsequently translocated by the G-protein beta-gamma complex to the plasma membrane. Here, the GTPase Cell division control protein 42 homolog (CDC42) binds with this complex. Subsequently, ARHGEF6 acts as a GEF for CDC42 and facilitates the activation of CDC42. CDC42 is known to be involved in epithelial cell polarization processes.
R-HSA-8964605 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. Serine/threonine-protein kinase PAK 1 binds with Rho guanine nucleotide exchange factor 6 (ARHGEF6, PIX-Alpha) in the cytosol. PAK1 in this complex then binds to G-protein beta-gamma complex and facilitates the translocation of PAK1:ARHGEF6 complex to the plasma membrane, where Cell division control protein 42 homolog (CDC42) is activated. CDC42 is known to be involved in epithelial cell polarization processes.
R-HSA-8964614 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. Serine/threonine-protein kinase PAK 1 binds with Rho guanine nucleotide exchange factor 6 (ARHGEF6, PIX-Alpha) in the cytosol and is subsequently translocated by the G-protein beta-gamma complex to the plasma membrane. Here, ARHGEF6 activates the GTPase Cell division control protein 42 homolog (CDC42) by acting as a GEF. Upon activation, CDC42 facilitates the activation of PAK1 by exposing its catalytic domains. PAK1 is a signalling entity playing a key role in cytoskeleton dynamics, cell adhesion, migration, proliferation, apoptosis, mitosis, and vesicle-mediated transport processes.
R-HSA-8964619 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. Serine/threonine-protein kinase PAK 1 can directly bind with Rho guanine nucleotide exchange factor 6 (ARHGEF6, PIX-Alpha) in the cytosol. This complex is then translocated to the plasma membrane where Cell division control protein 42 homolog (CDC42) is activated. CDC42 is known to be involved in epithelial cell polarization processes.
R-HSA-8964634 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. Serine/threonine-protein kinase PAK 1 binds with Rho guanine nucleotide exchange factor 6 (ARHGEF6, PIX-Alpha) in the cytosol and is subsequently translocated by the G-protein beta-gamma complex to the plasma membrane. Here, the GTPase Cell division control protein 42 homolog (CDC42) binds with this complex, following which ARHGEF6 activates CDC42. CDC42 is known to be involved in epithelial cell polarization processes.
R-HSA-9603279 (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.
RHOAR-HSA-202692 (Reactome)
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