G alpha (12/13) signaling events (Homo sapiens)

From WikiPathways

Jump to: navigation, search
8, 1352, 223, 10, 12, 15, 21244, 9, 2581114, 20, 27161, 6, 7195, 1718, 22, 24235cytosolRHOA GNA12 GNG12 Ligand:GPCRcomplexesthatactivateG12/13:Heterotrimeric G-protein G12/13 (inactive).ADRA1D GNGT2 GTP TXA2 GNA13 RHOC GNB4 ITSN1 GNGT1 GNG10 TBXA2R MCF2L RHOA:GTPADR, NAd GNG11 Ligands of GPCRsthat activateG12/13GNA13 GNG4 G-protein alpha(12/13):LARGVAV2 GNA12 GDPGNG8 GNG10 GNG11 Active BTK ROCK1,ROCK2:ROCKiARHGEF12RHOA/B/C:GTPGNA12 G-protein alpha(12/13):GTPARHGEF1 GPCRs that activateG12/13PLXNB1 ROCK1 RASGRF2 ARHGEF6 GNA12 GNB2 GNG7 Active BTKROCKiPREX1 GNG8 NET1 RHOA FGD1 GTPFGD4 ARHGEF1 GNA13 GNB3 GTP GNG2 VAV1 GTP ROCK1 GNB1 G13-activatedp115-RhoGEFROCK2 GNG7 G-protein alpha(12/13):GDPGNA13 GNB5 GDP ADR GNA13 ARHGEF37 GNG4 ADRA1A,B,D SOS1 GTPG-protein alpha(12/13):LARG:PlexinB1ADRA1D ROCK1 G-protein beta:gammasignallingARHGEF18 ADR ARHGEF17 GNGT2 BTKGNG3 GNG8 GEFsADRA1A GNA13 RHOA:GDPADRA1D GDPGNG12 ADRA1B GNG10 GDP ARHGEF40 RHOC ARHGEF3 GNA13 GDP ARHGEF4 RHOC ARHGEF12 GTP GNG4 ARHGEF33 GNG13 GNG7 GNB3 GTP GNG12 GNB3 Ligand:GPCRcomplexes thatactivate G12/13ARHGEF10L GNA13 ARHGEF5 G alpha (12):ActiveBTKGTP GNA13 GDP TIAM2 RHOA PLEKHG2 GNG13 ActivatedROCK:RhoA/B/C:GTPNAd G-protein G12/G13(inactive)ARHGEF1GNA12 RHOB GNA12 ARHGEF11 GNG13 GNA12 ADRA1B GNG7 Ligand:GPCRcomplexesthatactivateG12/13:Heterotrimeric G-protein G12/13 (active).TIAM1 ARHGEF15 ARHGEF2 ROCK2 ARHGEF38 SOS2 TBXA2R GNGT2 GTP GNGT1 GNG10 GNG11 GTP GNG13 GTP GTP ARHGEF9 FGD2 BTK G-protein beta-gammacomplexGNB4 ARHGEF10 AKAP13 GNB2 GNB1 GTP GNG8 ABR GNB2 GTP ARHGEF16 GNG2 GNB5 ARHGEF12 GNG11 GNB2 GNG3 ADRA1A GNG2 GNB4 PLEKHG5 GNA13 GTP NAd GDP ARHGEF35 TXA2 ARHGEF12 ARHGEF7 GNB1 GDPTXA2 TBXA2R ADRA1A GNGT1 KALRN G-protein alpha(13):GTPNGEF G-protein alpha(12):GTPECT2 ADR GNB5 ARHGEF26 GNB5 ROCK2 GNG3 GNG5 GNB1 PLXNB1GNG5 GNG4 GNB3 OBSCN GNA12 RHOA TBXA2R GNGT1 GNB4 GNG12 GNA12 RhoA,B,C:GDPGNG5 ADRA1B FGD3 RHOB ROCK1,ROCK2RHOB ARHGEF39 GNG3 GNG2 G alpha (12):BTKMCF2 VAV3 GTPTRIO TXA2 GNGT2 ARHGEF19 GNA12 GNG5 RHOA NAd 26


Description

The G12/13 family is probably the least well characterized subtype, partly because G12/13 coupling is difficult to determine when compared with the other subtypes which predominantly rely on assay technologies that measure intracellular calcium. The G12/13 family are best known for their involvement in the processes of cell proliferation and morphology, such as stress fiber and focal adhesion formation. Interactions with Rho guanine nucleotide exchange factors (RhoGEFs) are thought to mediate many of these processes. (Buhl et al.1995, Sugimoto et al. 2003). Activation of Rho or the regulation of events through Rho is often taken as evidence of G12/13 signaling. Receptors that are coupled with G12/13 invariably couple with one or more other G protein subtypes, usually Gq. View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 416482
Reactome-version 
Reactome version: 74
Reactome Author 
Reactome Author: Jupe, Steve

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Garnock-Jones KP.; ''Ripasudil: first global approval.''; PubMed Europe PMC Scholia
  2. Oldham WM, Hamm HE.; ''Structural basis of function in heterotrimeric G proteins.''; PubMed Europe PMC Scholia
  3. Araki S, Ito M, Kureishi Y, Feng J, Machida H, Isaka N, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T.; ''Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase.''; PubMed Europe PMC Scholia
  4. Maruyama Y, Nishida M, Sugimoto Y, Tanabe S, Turner JH, Kozasa T, Wada T, Nagao T, Kurose H.; ''Galpha(12/13) mediates alpha(1)-adrenergic receptor-induced cardiac hypertrophy.''; PubMed Europe PMC Scholia
  5. Jiang Y, Ma W, Wan Y, Kozasa T, Hattori S, Huang XY.; ''The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain.''; PubMed Europe PMC Scholia
  6. Sturdivant JM, Royalty SM, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong MA.; ''Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma.''; PubMed Europe PMC Scholia
  7. Tanna AP, Johnson M.; ''Rho Kinase Inhibitors as a Novel Treatment for Glaucoma and Ocular Hypertension.''; PubMed Europe PMC Scholia
  8. Suzuki N, Hajicek N, Kozasa T.; ''Regulation and physiological functions of G12/13-mediated signaling pathways.''; PubMed Europe PMC Scholia
  9. Nakahata N.; ''Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology.''; PubMed Europe PMC Scholia
  10. Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, Watanabe N, Saito Y, Kakizuka A, Morii N, Narumiya S.; ''The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase.''; PubMed Europe PMC Scholia
  11. Lambert NA.; ''Dissociation of heterotrimeric g proteins in cells.''; PubMed Europe PMC Scholia
  12. Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A, Olson MF.; ''Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I.''; PubMed Europe PMC Scholia
  13. Worzfeld T, Wettschureck N, Offermanns S.; ''G(12)/G(13)-mediated signalling in mammalian physiology and disease.''; PubMed Europe PMC Scholia
  14. Schmidt A, Hall A.; ''Guanine nucleotide exchange factors for Rho GTPases: turning on the switch.''; PubMed Europe PMC Scholia
  15. Leung T, Chen XQ, Manser E, Lim L.; ''The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton.''; PubMed Europe PMC Scholia
  16. Swiercz JM, Kuner R, Behrens J, Offermanns S.; ''Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology.''; PubMed Europe PMC Scholia
  17. 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
  18. Fukuhara S, Chikumi H, Gutkind JS.; ''RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?''; PubMed Europe PMC Scholia
  19. Suzuki N, Nakamura S, Mano H, Kozasa T.; ''Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF.''; PubMed Europe PMC Scholia
  20. Van Aelst L, D'Souza-Schorey C.; ''Rho GTPases and signaling networks.''; PubMed Europe PMC Scholia
  21. Sebbagh M, Hamelin J, Bertoglio J, Solary E, Bréard J.; ''Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner.''; PubMed Europe PMC Scholia
  22. Siderovski DP, Willard FS.; ''The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits.''; PubMed Europe PMC Scholia
  23. Kleuss C, Raw AS, Lee E, Sprang SR, Gilman AG.; ''Mechanism of GTP hydrolysis by G-protein alpha subunits.''; PubMed Europe PMC Scholia
  24. Chen Z, Guo L, Hadas J, Gutowski S, Sprang SR, Sternweis PC.; ''Activation of p115-RhoGEF requires direct association of Gα13 and the Dbl homology domain.''; PubMed Europe PMC Scholia
  25. Riobo NA, Manning DR.; ''Receptors coupled to heterotrimeric G proteins of the G12 family.''; PubMed Europe PMC Scholia
  26. 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
  27. Jaffe AB, Hall A.; ''Rho GTPases: biochemistry and biology.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
116406view09:03, 7 May 2021EweitzModified title
113255view11:32, 2 November 2020ReactomeTeamReactome version 74
101711view14:51, 1 November 2018DeSlOntology Term : 'G protein mediated signaling pathway via Galpha12/Galpha13 family' added !
101382view11:27, 1 November 2018ReactomeTeamreactome version 66
100920view21:02, 31 October 2018ReactomeTeamreactome version 65
100461view19:37, 31 October 2018ReactomeTeamreactome version 64
100275view16:57, 31 October 2018ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ABR ProteinQ12979 (Uniprot-TrEMBL)
ADR MetaboliteCHEBI:28918 (ChEBI)
ADR, NAd R-ALL-390627 (Reactome)
ADRA1A ProteinP35348 (Uniprot-TrEMBL)
ADRA1A,B,D R-HSA-390684 (Reactome)
ADRA1B ProteinP35368 (Uniprot-TrEMBL)
ADRA1D ProteinP25100 (Uniprot-TrEMBL)
AKAP13 ProteinQ12802 (Uniprot-TrEMBL)
ARHGEF1 ProteinQ92888 (Uniprot-TrEMBL)
ARHGEF10 ProteinO15013 (Uniprot-TrEMBL)
ARHGEF10L ProteinQ9HCE6 (Uniprot-TrEMBL)
ARHGEF11 ProteinO15085 (Uniprot-TrEMBL)
ARHGEF12 ProteinQ9NZN5 (Uniprot-TrEMBL)
ARHGEF12ProteinQ9NZN5 (Uniprot-TrEMBL)
ARHGEF15 ProteinO94989 (Uniprot-TrEMBL)
ARHGEF16 ProteinQ5VV41 (Uniprot-TrEMBL)
ARHGEF17 ProteinQ96PE2 (Uniprot-TrEMBL)
ARHGEF18 ProteinQ6ZSZ5 (Uniprot-TrEMBL)
ARHGEF19 ProteinQ8IW93 (Uniprot-TrEMBL)
ARHGEF1ProteinQ92888 (Uniprot-TrEMBL)
ARHGEF2 ProteinQ92974 (Uniprot-TrEMBL)
ARHGEF26 ProteinQ96DR7 (Uniprot-TrEMBL)
ARHGEF3 ProteinQ9NR81 (Uniprot-TrEMBL)
ARHGEF33 ProteinA8MVX0 (Uniprot-TrEMBL)
ARHGEF35 ProteinA5YM69 (Uniprot-TrEMBL)
ARHGEF37 ProteinA1IGU5 (Uniprot-TrEMBL)
ARHGEF38 ProteinQ9NXL2 (Uniprot-TrEMBL)
ARHGEF39 ProteinQ8N4T4 (Uniprot-TrEMBL)
ARHGEF4 ProteinQ9NR80 (Uniprot-TrEMBL)
ARHGEF40 ProteinQ8TER5 (Uniprot-TrEMBL)
ARHGEF5 ProteinQ12774 (Uniprot-TrEMBL)
ARHGEF6 ProteinQ15052 (Uniprot-TrEMBL)
ARHGEF7 ProteinQ14155 (Uniprot-TrEMBL)
ARHGEF9 ProteinO43307 (Uniprot-TrEMBL)
Activated ROCK:RhoA/B/C:GTPComplexR-HSA-422483 (Reactome)
Active BTK ProteinQ06187 (Uniprot-TrEMBL)
Active BTKProteinQ06187 (Uniprot-TrEMBL)
BTK ProteinQ06187 (Uniprot-TrEMBL)
BTKProteinQ06187 (Uniprot-TrEMBL)
ECT2 ProteinQ9H8V3 (Uniprot-TrEMBL)
FGD1 ProteinP98174 (Uniprot-TrEMBL)
FGD2 ProteinQ7Z6J4 (Uniprot-TrEMBL)
FGD3 ProteinQ5JSP0 (Uniprot-TrEMBL)
FGD4 ProteinQ96M96 (Uniprot-TrEMBL)
G alpha (12):Active BTKComplexR-HSA-8964299 (Reactome)
G alpha (12):BTKComplexR-HSA-8964310 (Reactome)
G-protein G12/G13 (inactive)ComplexR-HSA-398082 (Reactome)
G-protein alpha (12):GTPComplexR-HSA-114525 (Reactome)
G-protein alpha (12/13):GDPComplexR-HSA-418570 (Reactome)
G-protein alpha (12/13):GTPComplexR-HSA-418572 (Reactome)
G-protein alpha

(12/13):LARG:Plexin

B1
ComplexR-HSA-398146 (Reactome)
G-protein alpha (12/13):LARGComplexR-HSA-398145 (Reactome) Phospholipase C activation is the classical signalling route for G alpha (q) but an additional mechanism is an inhibitory interaction between G alpha (q) and phosphatidylinositol 3-kinase alpha (PI3K alpha). There are several PI3K subtypes but only the p85 alpha/p110 alpha subtype (PI3K alpha) is a G alpha (q) effector (PMID: 18515384). Activated G alpha (q) inhibits PI3K alpha directly, in a GTP-dependent manner. G alpha(q) binding of PI3K competes with Ras, a PI3K activator (PMID: 16268778).
G-protein alpha (13):GTPComplexR-HSA-398056 (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.
G13-activated p115-RhoGEFComplexR-HSA-114527 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GEFsComplexR-HSA-194849 (Reactome)
GNA12 ProteinQ03113 (Uniprot-TrEMBL)
GNA13 ProteinQ14344 (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)
GPCRs that activate G12/13ComplexR-HSA-791500 (Reactome)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
ITSN1 ProteinQ15811 (Uniprot-TrEMBL)
KALRN ProteinO60229 (Uniprot-TrEMBL)
Ligand:GPCR

complexes that activate

G12/13:Heterotrimeric G-protein G12/13 (active).
ComplexR-HSA-751015 (Reactome)
Ligand:GPCR

complexes that activate

G12/13:Heterotrimeric G-protein G12/13 (inactive).
ComplexR-HSA-750994 (Reactome)
Ligand:GPCR

complexes that

activate G12/13
ComplexR-HSA-751003 (Reactome)
Ligands of GPCRs

that activate

G12/13
ComplexR-ALL-791498 (Reactome)
MCF2 ProteinP10911 (Uniprot-TrEMBL)
MCF2L ProteinO15068 (Uniprot-TrEMBL)
NAd MetaboliteCHEBI:18357 (ChEBI)
NET1 ProteinQ7Z628 (Uniprot-TrEMBL)
NGEF ProteinQ8N5V2 (Uniprot-TrEMBL)
OBSCN ProteinQ5VST9 (Uniprot-TrEMBL)
PLEKHG2 ProteinQ9H7P9 (Uniprot-TrEMBL)
PLEKHG5 ProteinO94827 (Uniprot-TrEMBL)
PLXNB1 ProteinO43157 (Uniprot-TrEMBL)
PLXNB1ProteinO43157 (Uniprot-TrEMBL)
PREX1 ProteinQ8TCU6 (Uniprot-TrEMBL)
RASGRF2 ProteinO14827 (Uniprot-TrEMBL)
RHOA ProteinP61586 (Uniprot-TrEMBL)
RHOA/B/C:GTPComplexR-HSA-419161 (Reactome)
RHOA:GDPComplexR-HSA-8964174 (Reactome)
RHOA:GTPComplexR-HSA-5665993 (Reactome)
RHOB ProteinP62745 (Uniprot-TrEMBL)
RHOC ProteinP08134 (Uniprot-TrEMBL)
ROCK1 ProteinQ13464 (Uniprot-TrEMBL)
ROCK1,ROCK2:ROCKiComplexR-HSA-9680444 (Reactome)
ROCK1,ROCK2ComplexR-HSA-419057 (Reactome) ROCK I (alternatively called ROK ?) and ROCK II (also known as Rho kinase or ROK ?) were originally isolated as RhoA-GTP interacting proteins. The kinase domains of ROCK I and ROCK II are 92% identical, and so far there is no evidence that they phosphorylate different substrates. RhoA, RhoB, and RhoC associate with and activate ROCK but other GTP-binding proteins can be inhibitors, e.g. RhoE, Rad and Gem. PDK1 kinase promotes ROCK I activity not through phosphorylation but by blocking RhoE association. PLK1 can phosphorylate ROCK II and this enhances the effect of RhoA. Arachidonic acid can activate ROCK independently of Rho.
ROCK2 ProteinO75116 (Uniprot-TrEMBL)
ROCKiComplexR-ALL-9686558 (Reactome)
RhoA,B,C:GDPComplexR-HSA-419164 (Reactome)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
SOS2 ProteinQ07890 (Uniprot-TrEMBL)
TBXA2R ProteinP21731 (Uniprot-TrEMBL)
TIAM1 ProteinQ13009 (Uniprot-TrEMBL)
TIAM2 ProteinQ8IVF5 (Uniprot-TrEMBL)
TRIO ProteinO75962 (Uniprot-TrEMBL)
TXA2 MetaboliteCHEBI:15627 (ChEBI)
VAV1 ProteinP15498 (Uniprot-TrEMBL)
VAV2 ProteinP52735 (Uniprot-TrEMBL)
VAV3 ProteinQ9UKW4 (Uniprot-TrEMBL)
ripasudil

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ARHGEF12R-HSA-398184 (Reactome)
ARHGEF1R-HSA-114548 (Reactome)
Activated ROCK:RhoA/B/C:GTPArrowR-HSA-419049 (Reactome)
Active BTKArrowR-HSA-8964333 (Reactome)
BTKR-HSA-8964274 (Reactome)
G alpha (12):Active BTKArrowR-HSA-8964246 (Reactome)
G alpha (12):Active BTKR-HSA-8964333 (Reactome)
G alpha (12):BTKArrowR-HSA-8964274 (Reactome)
G alpha (12):BTKR-HSA-8964246 (Reactome)
G-protein G12/G13 (inactive)ArrowR-HSA-751039 (Reactome)
G-protein G12/G13 (inactive)R-HSA-751027 (Reactome)
G-protein alpha (12):GTPArrowR-HSA-8964333 (Reactome)
G-protein alpha (12):GTPR-HSA-8964274 (Reactome)
G-protein alpha (12/13):GDPArrowR-HSA-418574 (Reactome)
G-protein alpha (12/13):GDPR-HSA-751039 (Reactome)
G-protein alpha (12/13):GTPArrowR-HSA-751019 (Reactome)
G-protein alpha (12/13):GTPR-HSA-398184 (Reactome)
G-protein alpha (12/13):GTPR-HSA-418574 (Reactome)
G-protein alpha (12/13):GTPmim-catalysisR-HSA-418574 (Reactome)
G-protein alpha

(12/13):LARG:Plexin

B1
ArrowR-HSA-398185 (Reactome)
G-protein alpha (12/13):LARGArrowR-HSA-398184 (Reactome)
G-protein alpha (12/13):LARGR-HSA-398185 (Reactome)
G-protein alpha (13):GTPR-HSA-114548 (Reactome)
G-protein beta-gamma complexArrowR-HSA-751019 (Reactome)
G-protein beta-gamma complexR-HSA-751039 (Reactome)
G13-activated p115-RhoGEFArrowR-HSA-114548 (Reactome)
G13-activated p115-RhoGEFmim-catalysisR-HSA-114544 (Reactome)
GDPArrowR-HSA-114544 (Reactome)
GDPArrowR-HSA-419166 (Reactome)
GDPArrowR-HSA-751029 (Reactome)
GEFsmim-catalysisR-HSA-419166 (Reactome)
GPCRs that activate G12/13ArrowR-HSA-751019 (Reactome)
GTPR-HSA-114544 (Reactome)
GTPR-HSA-419166 (Reactome)
GTPR-HSA-751029 (Reactome)
Ligand:GPCR

complexes that activate

G12/13:Heterotrimeric G-protein G12/13 (active).
ArrowR-HSA-751029 (Reactome)
Ligand:GPCR

complexes that activate

G12/13:Heterotrimeric G-protein G12/13 (active).
R-HSA-751019 (Reactome)
Ligand:GPCR

complexes that activate

G12/13:Heterotrimeric G-protein G12/13 (inactive).
ArrowR-HSA-751027 (Reactome)
Ligand:GPCR

complexes that activate

G12/13:Heterotrimeric G-protein G12/13 (inactive).
R-HSA-751029 (Reactome)
Ligand:GPCR

complexes that activate

G12/13:Heterotrimeric G-protein G12/13 (inactive).
mim-catalysisR-HSA-751029 (Reactome)
Ligand:GPCR

complexes that

activate G12/13
R-HSA-751027 (Reactome)
Ligands of GPCRs

that activate

G12/13
ArrowR-HSA-751019 (Reactome)
PLXNB1R-HSA-398185 (Reactome)
R-HSA-114544 (Reactome) ARHEF1 (p115-RhoGEF), recruited to the plasma membrane by binding to GTP-bound G-protein alpha (13) (GNA13), stimulates GDP to GTP exchange on RHOA, resulting in activation of the RHOA GTPase (Chen et al. 2012).
R-HSA-114548 (Reactome) p115-RhoGEF is a potent GTPase activating protein (GAP) for both G alpha 12 and G alpha 13 subunits. More importantly, the interaction between activated G alpha 13 (but not G alpha 12) triggers p115-RhoGEF activity. While this pathway may be important in vivo, in prostate-derived PC-3 cells RNAi mediated knockdown of p115-RhoGEF levels had no effect on the response to thrombin (Wang et al. 2004).
R-HSA-398184 (Reactome) Leukemia-associated RhoGEF (LARG) serves as a G alpha responsive RhoGEF for G alpha 12, 13 and possibly G alpha q. G alpha 12 activity appears to depend on LARG tyrosine phosphorylation by Tec-family kinases (Suzuki et al. 2003) or FAK (Chikumi et al. 2002). The involvement of LARG may be specific to particular receptor signalling pathways; RNAi-mediated knockdown of LARG specifically inhibited thrombin signaling via PAR1 but not LPA receptors (Wang et al 2004).
R-HSA-398185 (Reactome) LARG binds plexin-B1, a transmembrane receptor for the semaphorin Sema4D. Binding of Sema4D to plexin-B1 stimulates RhoA activation.
R-HSA-418574 (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-419049 (Reactome) ROCKs are primarily known as downstream effectors of RHO, but they can also be activated by arachidonic acid, which binds to the pleckstrin homology domain, releasing an autoinhibitory loop within ROCK and allowing catalytic activity (Araki et al. 2001). Proteolytic cleavage at the C-terminus by caspase-3 and granzyme B also activates ROCK1 and ROCK2, causing plasma membrane blebbing during apoptosis (Coleman et al. 2001, Sebbagh et al. 2005). Multiple targets of ROCK contribute to the stabilization of actin filaments and the generation of actin-myosin contractile force.
R-HSA-419166 (Reactome) Guanine nucleotide exchange factors (GEFs) activate GTPases by enhancing the exchange of bound GDP for GTP. Much evidence points to GEFs being critical mediators of Rho GTPase activation (Schmidt and Hall, 2002). Many GEFs are known to be highly specific for a particular GTPase, e.g. Fgd1/Cdc42 and p115RhoGEF/Rho (Hart et al., 1996, Zheng et al., 1996). Others have a broader spectrum and activate several GTPases, e.g. Vav1 for Rac, Rho, and Cdc42 (Hart et al, 1994).
R-HSA-751019 (Reactome) The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. Activated G alpha (12/13) 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-751027 (Reactome) About 25 receptors are reported to couple to the G12/13 G protein subtype (Riobo & Manning, 2005).Direct assay methods have not identified a receptor that only couples with G12. At least one receptor (5-HT4) only couples with G13, but most other receptors are reported to couple with both G12 and G13.
R-HSA-751029 (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-751039 (Reactome) The classical model of G-protein signaling suggests that the G-protein dissociates upon GPCR activation. The active alpha subunit then participates in signaling, until its intrinsic GTPase activity degrades the bound GTP to GDP. The inactive G alpha (12/13):GDP complex has much higher affinity for the G beta:gamma complex and consequently reassociates into the inactive heterotrimeric G-protein.
R-HSA-8964246 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins. Upon activation, the Guanine nucleotide-binding protein subunit alpha-12 (GNA12) can bind the non-receptor Tyrosine-protein kinase BTK. In this complex, GNA12 triggers BTK activation. Physiologically, BTK plays a key role in B lymphocyte development, differentiation and signalling.
R-HSA-8964274 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins. Upon activation, the Guanine nucleotide-binding protein subunit alpha-12 (GNA12) can bind directly to the PH domain of the non-receptor Tyrosine-protein kinase BTK (BTK) in vitro and in vivo. This binding results in the activation of BTK. Physiologically, BTK plays a key role in B lymphocyte development, differentiation and signalling.
R-HSA-8964333 (Reactome) G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins. Upon activation, the Guanine nucleotide-binding protein subunit alpha-12 (GNA12) can bind to the non-receptor Tyrosine-protein kinase BTK. This complex facilitates BTK activation. Subsequently, the active BTK dissociates from GNA12 to phosphorylate downstream effectors. Physiologically, BTK plays a key role in B lymphocyte development, differentiation and signalling.
R-HSA-9680443 (Reactome) Ripasudil (Glanatec), as its hydrochloride hydrate (K-115), is a specifc Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor (ROCKi) used for the treatment of glaucoma and ocular hypertension in Japan (Garnock-Jones 2014). Netarsudil is a USA-approved ROCKi used to treat glaucoma and ocular hypertenstion (Sturdivant et al. 2016, Tanna & Johnson 2018).
RHOA/B/C:GTPArrowR-HSA-419166 (Reactome)
RHOA/B/C:GTPR-HSA-419049 (Reactome)
RHOA:GDPR-HSA-114544 (Reactome)
RHOA:GTPArrowR-HSA-114544 (Reactome)
ROCK1,ROCK2:ROCKiArrowR-HSA-9680443 (Reactome)
ROCK1,ROCK2:ROCKiTBarR-HSA-419049 (Reactome)
ROCK1,ROCK2R-HSA-419049 (Reactome)
ROCK1,ROCK2R-HSA-9680443 (Reactome)
ROCKiR-HSA-9680443 (Reactome)
RhoA,B,C:GDPR-HSA-419166 (Reactome)
Personal tools