BioPAX pathway converted from "G alpha (12/13) signalling events" in the Reactome database. G alpha (12/13) signalling events G alpha (12/13) signalling events This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Liganded G12/13-activating GPCRs bind inactive heterotrimeric G-protein G12/13 Liganded G12/13-activating GPCRs bind inactive heterotrimeric G-protein G12/13 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10608544 1 plasma membrane GO 0005886 Ligand:GPCR complexes that activate G12/13 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome http://www.reactome.org Converted from EntitySet in Reactome Reactome DB_ID: 10585153 1 G-protein G12/G13 (inactive) [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 10608554 1 Ligand:GPCR complexes that activate G12/13:Heterotrimeric G-protein G12/13 (inactive). [plasma membrane] Ligand:GPCR complexes that activate G12/13:Heterotrimeric G-protein G12/13 (inactive). Converted from EntitySet in Reactome Reactome DB_ID: 10608544 1 Converted from EntitySet in Reactome Reactome DB_ID: 10585153 1 Gallus gallus NCBI Taxonomy 9031 Reactome Database ID Release 83 10608554 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10608554 Reactome R-GGA-750994 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-750994.1 Reactome Database ID Release 83 10608556 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10608556 Reactome R-GGA-751027 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-751027.1 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. 12433842 Pubmed 2002 Galpha(12/13) mediates alpha(1)-adrenergic receptor-induced cardiac hypertrophy Maruyama, Y Nishida, M Sugimoto, Y Tanabe, S Turner, JH Kozasa, T Wada, T Nagao, T Kurose, H Circ Res 91:961-9 18374420 Pubmed 2008 Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology Nakahata, N Pharmacol Ther 118:18-35 15749160 Pubmed 2005 Receptors coupled to heterotrimeric G proteins of the G12 family Riobo, NA Manning, DR Trends Pharmacol Sci 26:146-54 inferred by electronic annotation IEA GO IEA Liganded G12/13-activating GPCR acts as a GEF for G12/13 Liganded G12/13-activating GPCR acts as a GEF for G12/13 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10608554 1 Reactome DB_ID: 29438 1 cytosol GO 0005829 GTP(4-) [ChEBI:37565] GTP(4-) GTP gtp guanosine 5'-triphosphate(4-) ChEBI 37565 Reactome DB_ID: 29420 1 GDP(3-) [ChEBI:58189] GDP(3-) guanosine 5'-diphosphate(3-) 5'-O-[(phosphonatooxy)phosphinato]guanosine guanosine 5'-diphosphate trianion GDP GDP trianion guanosine 5'-diphosphate ChEBI 58189 Reactome DB_ID: 10608546 1 Ligand:GPCR complexes that activate G12/13:Heterotrimeric G-protein G12/13 (active). [plasma membrane] Ligand:GPCR complexes that activate G12/13:Heterotrimeric G-protein G12/13 (active). Converted from EntitySet in Reactome Reactome DB_ID: 10608544 1 Converted from EntitySet in Reactome Reactome DB_ID: 10585163 1 G-protein G12/G13 (active) [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome Database ID Release 83 10608546 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10608546 Reactome R-GGA-751015 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-751015.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10608554 GO 0005085 GO molecular function Reactome Database ID Release 83 10608557 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10608557 Reactome Database ID Release 83 10608559 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10608559 Reactome R-GGA-751029 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-751029.1 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). 3086311 Pubmed 1986 The influence of bound GDP on the kinetics of guanine nucleotide binding to G proteins Ferguson, KM Higashijima, T Smigel, MD Gilman, AG J Biol Chem 261:7393-9 11024022 Pubmed 2000 AGS3 inhibits GDP dissociation from galpha subunits of the Gi family and rhodopsin-dependent activation of transducin Natochin, M Lester, B Peterson, Y K Bernard, M L Lanier, S M Artemyev, NO J. Biol. Chem. 275:40981-5 12860983 Pubmed 2003 Oxidized human neuroglobin acts as a heterotrimeric Galpha protein guanine nucleotide dissociation inhibitor Wakasugi, Keisuke Nakano, Tomomi Morishima, Isao J. Biol. Chem. 278:36505-12 18434541 Pubmed 2008 Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits Soundararajan, Meera Willard, Francis S Kimple, Adam J Turnbull, Andrew P Ball, Linda J Schoch, Guillaume A Gileadi, Carina Fedorov, Oleg Y Dowler, Elizabeth F Higman, Victoria A Hutsell, Stephanie Q Sundström, M Doyle, DA Siderovski, David P Proc. Natl. Acad. Sci. U.S.A. 105:6457-62 3113327 Pubmed 1987 G proteins: transducers of receptor-generated signals Gilman, AG Annu Rev Biochem 56:615-49 9032437 Pubmed 1997 Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins Fields, TA Casey, PJ Biochem J 321:561-71 8973305 Pubmed 1996 Identification and cDNA cloning of a novel human mosaic protein, LGN, based on interaction with G alpha i2 Mochizuki, N Cho, G Wen, B Insel, P A Gene 181:39-43 10559191 Pubmed 1999 Receptor-independent activators of heterotrimeric G-protein signaling pathways Takesono, A Cismowski, M J Ribas, C Bernard, M Chung, P Hazard, S Duzic, E Lanier, S M J. Biol. Chem. 274:33202-5 10471929 Pubmed 1999 Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling Cismowski, M J Takesono, A Ma, C Lizano, J S Xie, X Fuernkranz, H Lanier, S M Duzic, E Nat. Biotechnol. 17:878-83 10969064 Pubmed 2000 Stabilization of the GDP-bound conformation of Gialpha by a peptide derived from the G-protein regulatory motif of AGS3 Peterson, Y K Bernard, M L Ma, H Hazard, S Graber, S G Lanier, S M J. Biol. Chem. 275:33193-6 24302560 Pubmed 2014 Activators of G protein signaling exhibit broad functionality and define a distinct core signaling triad Blumer, Joe B Lanier, Stephen M Mol. Pharmacol. 85:388-96 19212140 Pubmed 2009 Regulation and physiological functions of G12/13-mediated signaling pathways Suzuki, N Hajicek, N Kozasa, T Neurosignals 17:55-70 15096500 Pubmed 2004 Identification and characterization of AGS4: a protein containing three G-protein regulatory motifs that regulate the activation state of Gialpha Cao, Xiaoqing Cismowski, Mary J Sato, Motohiko Blumer, Joe B Lanier, Stephen M J. Biol. Chem. 279:27567-74 inferred by electronic annotation IEA GO IEA The Ligand:GPCR:G12/13 complex dissociates The Ligand:GPCR:G12/13 complex dissociates This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10608546 1 Converted from EntitySet in Reactome Reactome DB_ID: 791498 1 extracellular region GO 0005576 Ligands of GPCRs that activate G12/13 [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ADR [extracellular region] NAd [extracellular region] TXA2 [extracellular region] ChEBI 71406 ChEBI 72587 ChEBI 15627 Converted from EntitySet in Reactome Reactome DB_ID: 10608548 1 GPCRs that activate G12/13 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ADRA1A [plasma membrane] ADRA1B [plasma membrane] ADRA1D [plasma membrane] TBXA2R [plasma membrane] UniProt F1NP52 UniProt F1NIZ5 UniProt A0A1D5PRZ3 UniProt A0A1D5P7R6 Converted from EntitySet in Reactome Reactome DB_ID: 10602549 1 G-protein alpha (12/13):GTP [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 10584699 2 G-protein beta-gamma complex [plasma membrane] G-protein beta-gamma complex Converted from EntitySet in Reactome Reactome DB_ID: 10584679 1 G-protein gamma subunit [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GNG2 [plasma membrane] UniProt Q5ZJ03 Converted from EntitySet in Reactome Reactome DB_ID: 10584697 1 G-protein beta subunit [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GNB1 [cytosol] UniProt F1NLV4 Reactome Database ID Release 83 10584699 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10584699 Reactome R-GGA-167434 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-167434.1 Reactome Database ID Release 83 10608550 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10608550 Reactome R-GGA-751019 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-751019.1 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). 18577758 Pubmed 2008 Dissociation of heterotrimeric g proteins in cells Lambert, NA Sci Signal 1:re5 inferred by electronic annotation IEA GO IEA GEFs activate RhoA,B,C GEFs activate RhoA,B,C This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10603011 1 RhoA,B,C:GDP [plasma membrane] RhoA,B,C:GDP Reactome DB_ID: 114549 1 GDP [ChEBI:17552] GDP Guanosine 5'-diphosphate Guanosine diphosphate ChEBI 17552 Converted from EntitySet in Reactome Reactome DB_ID: 10603009 1 RHOA/B/C [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity cRhoA [plasma membrane] RHOC [plasma membrane] cRhoB [plasma membrane] UniProt O93467 UniProt Q9PSX7 UniProt O93468 Reactome Database ID Release 83 10603011 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603011 Reactome R-GGA-419164 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419164.1 Reactome DB_ID: 29438 1 Reactome DB_ID: 29420 1 Reactome DB_ID: 10603013 1 RHOA/B/C:GTP [plasma membrane] RHOA/B/C:GTP Converted from EntitySet in Reactome Reactome DB_ID: 10603009 1 Reactome DB_ID: 29438 1 Reactome Database ID Release 83 10603013 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603013 Reactome R-GGA-419161 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419161.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10596129 GEFs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity TRIO [cytosol] AKAP13 [cytosol] ITSN1 [cytosol] KALRN [cytosol] ECT2 [cytosol] ARHGEF11 [cytosol] ARHGEF7 [cytosol] ARHGEF26 [cytosol] OBSL1 [cytosol] PLEKHG5 [cytosol] RASGRF2 [cytosol] FGD3 [cytosol] ARHGEF12 [cytosol] NGEF [cytosol] ARHGEF3 [cytosol] MCF2 [cytosol] VAV3 [cytosol] SOS1 [cytosol] ARHGEF6 [cytosol] TIAM1 [cytosol] SOS2 [cytosol] VAV2 [cytosol] ARHGEF17 [cytosol] TIAM2 [cytosol] FGD4 [cytosol] ARHGEF9 [cytosol] MCF2L [cytosol] NET1 [cytosol] ABR [cytosol] ARHGEF5 [cytosol] ARHGEF16 [cytosol] PREX1 [cytosol] UniProt A0A1D5NZW8 UniProt F1NIT0 UniProt A0A1D5P467 UniProt A0A1D5PRH4 UniProt E1BWT7 UniProt A0A1D5PNR3 UniProt A0A3Q2TZR1 UniProt F1NBE4 UniProt F1P369 UniProt A0A1D5PX49 UniProt F1ND09 UniProt A0A1D5NVP9 UniProt F1P1Y1 UniProt A0A1D5NXP9 UniProt A0A3Q2U9N5 UniProt E1BWQ1 UniProt Q8UUX6 UniProt A0A1D5PEZ2 UniProt F1NEF5 UniProt A0A1D5P0C4 UniProt F1N8Q9 UniProt A0A1D5NVQ5 UniProt E1C588 UniProt A0A1D5PML9 UniProt A0A3Q2TZP0 UniProt A0A3Q2U0A5 UniProt R4GL74 UniProt Q5ZJM0 UniProt A0A1D5NWU3 UniProt E1C6J2 UniProt E1BQT7 UniProt A0A3Q2U7M9 Reactome Database ID Release 83 10596130 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10596130 Reactome Database ID Release 83 10603421 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603421 Reactome R-GGA-419166 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419166.1 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). 8810315 Pubmed 1996 Identification of a novel guanine nucleotide exchange factor for the Rho GTPase Hart, MJ Sharma, S elMasry, N Qiu, RG McCabe, P Polakis, P Bollag, G J Biol Chem 271:25452-8 16212495 Pubmed 2005 Rho GTPases: biochemistry and biology Jaffe, AB Hall, A Annu Rev Cell Dev Biol 21:247-69 9308960 Pubmed 1997 Rho GTPases and signaling networks Van Aelst, L D'Souza-Schorey, C Genes Dev 11:2295-322 8276860 Pubmed 1994 Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product Hart, MJ Eva, A Zangrilli, D Aaronson, Stuart A Evans, T Cerione, RA Zheng, Y J Biol Chem 269:62-5 12101119 Pubmed 2002 Guanine nucleotide exchange factors for Rho GTPases: turning on the switch Schmidt, A Hall, A Genes Dev 16:1587-609 inferred by electronic annotation IEA GO IEA ROCK activation by RHO ROCK activation by RHO This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10603412 1 ROCK1,ROCK2 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ROCK2 [cytosol] ROCK1 [cytosol] UniProt A0A3Q2TTH6 UniProt A0A1D5PK41 Reactome DB_ID: 10603013 1 Reactome DB_ID: 10603414 1 Activated ROCK:RhoA/B/C:GTP [plasma membrane] Activated ROCK:RhoA/B/C:GTP Converted from EntitySet in Reactome Reactome DB_ID: 10603412 1 Reactome DB_ID: 10603013 1 Reactome Database ID Release 83 10603414 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603414 Reactome R-GGA-422483 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-422483.1 Reactome Database ID Release 83 10603418 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603418 Reactome R-GGA-419049 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419049.1 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. 11294240 Pubmed 2001 Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase Araki, S Ito, M Kureishi, Y Feng, J Machida, H Isaka, N Amano, M Kaibuchi, K Hartshorne, D J Nakano, T Pflugers Arch. 441:596-603 8617235 Pubmed 1996 The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase Ishizaki, T Maekawa, M Fujisawa, K Okawa, K Iwamatsu, A Fujita, A Watanabe, Nobumoto Saito, Y Kakizuka, A Morii, N Narumiya, S EMBO J 15:1885-93 8816443 Pubmed 1996 The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton Leung, T Chen, X Q Manser, E Lim, L Mol. Cell. Biol. 16:5313-27 15699075 Pubmed 2005 Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner Sebbagh, Michael Hamelin, Jocelyne Bertoglio, Jacques Solary, Eric Breard, Jacqueline J. Exp. Med. 201:465-71 12778124 Pubmed 2003 Rocks: multifunctional kinases in cell behaviour Riento, K Ridley, AJ Nat Rev Mol Cell Biol 4:446-56 9920927 Pubmed 1999 Rho-associated kinase of chicken gizzard smooth muscle Feng, J Ito, M Kureishi, Y Ichikawa, K Amano, M Isaka, N Okawa, K Iwamatsu, A Kaibuchi, K Hartshorne, DJ Nakano, T J Biol Chem 274:3744-52 11283606 Pubmed 2001 Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I Coleman, M L Sahai, E A Yeo, M Bosch, M Dewar, A Olson, M F Nat. Cell Biol. 3:339-45 inferred by electronic annotation IEA GO IEA INHIBITION Reactome Database ID Release 83 10603419 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603419 Reactome DB_ID: 10603416 ROCK1,ROCK2:ROCKi [cytosol] ROCK1,ROCK2:ROCKi Converted from EntitySet in Reactome Reactome DB_ID: 10603412 1 Converted from EntitySet in Reactome Reactome DB_ID: 9686558 1 ROCKi [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ripasudil [cytosol] netarsudil [cytosol] Guide to Pharmacology 10423 Guide to Pharmacology 9322 Reactome Database ID Release 83 10603416 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603416 Reactome R-GGA-9680444 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-9680444.1 ROCK1,2 bind ROCKi ROCK1,2 bind ROCKi This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10603412 1 Converted from EntitySet in Reactome Reactome DB_ID: 9686558 1 Reactome DB_ID: 10603416 1 Reactome Database ID Release 83 10664542 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10664542 Reactome R-GGA-9680443 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-9680443.1 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). 25414122 Pubmed 2014 Ripasudil: first global approval Garnock-Jones, Karly P Drugs 74:2211-5 27072905 Pubmed 2016 Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma Sturdivant, Jill M Royalty, Susan M Lin, Cheng-Wen Moore, Lori A Yingling, Jeffrey D Laethem, Carmen L Sherman, Bryan Heintzelman, Geoffrey R Kopczynski, Casey C deLong, Mitchell A Bioorg. Med. Chem. Lett. 26:2475-2480 30007591 Pubmed 2018 Rho Kinase Inhibitors as a Novel Treatment for Glaucoma and Ocular Hypertension Tanna, Angelo P Johnson, Mark Ophthalmology 125:1741-1756 inferred by electronic annotation IEA GO IEA LARG activation by G alpha 12/13 LARG activation by G alpha 12/13 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10602549 1 Reactome DB_ID: 10596063 1 UniProt:F1P1Y1 ARHGEF12 Chain Coordinates 1 EQUAL 1544 EQUAL Reactome DB_ID: 10602559 1 G-protein alpha (12/13):LARG [plasma membrane] G-protein alpha (12/13):LARG Converted from EntitySet in Reactome Reactome DB_ID: 10602549 1 Reactome DB_ID: 10596063 1 1 EQUAL 1544 EQUAL Reactome Database ID Release 83 10602559 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10602559 Reactome R-GGA-398145 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-398145.1 Reactome Database ID Release 83 10602561 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10602561 Reactome R-GGA-398184 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-398184.1 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). 11799111 Pubmed 2002 Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinase Chikumi, H Fukuhara, S Gutkind, JS J Biol Chem 277:12463-73 15951850 Pubmed 2005 The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits Siderovski, DP Willard, FS Int J Biol Sci 1:51-66 15143072 Pubmed 2004 Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells Wang, Q Liu, M Kozasa, T Rothstein, JD Sternweis, PC Neubig, RR J Biol Chem 279:28831-4 12515866 Pubmed 2003 Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF Suzuki, N Nakamura, S Mano, H Kozasa, T Proc Natl Acad Sci U S A 100:733-8 12771155 Pubmed 2003 Receptor-dependent RhoA activation in G12/G13-deficient cells: genetic evidence for an involvement of Gq/G11 Vogt, S Grosse, R Schultz, G Offermanns, S J Biol Chem 278:28743-9 inferred by electronic annotation IEA GO IEA LARG binds plexin B1 LARG binds plexin B1 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10602559 1 Reactome DB_ID: 10598677 1 UniProt:A0A3Q2TW45 PLXNB3 UniProt A0A3Q2TW45 20 EQUAL 2135 EQUAL Reactome DB_ID: 10602563 1 G-protein alpha (12/13):LARG:Plexin B1 [plasma membrane] G-protein alpha (12/13):LARG:Plexin B1 Reactome DB_ID: 10602559 1 Reactome DB_ID: 10598677 1 20 EQUAL 2135 EQUAL Reactome Database ID Release 83 10602563 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10602563 Reactome R-GGA-398146 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-398146.1 Reactome Database ID Release 83 10602565 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10602565 Reactome R-GGA-398185 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-398185.1 LARG binds plexin-B1, a transmembrane receptor for the semaphorin Sema4D. Binding of Sema4D to plexin-B1 stimulates RhoA activation. 12123608 Pubmed 2002 Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology Swiercz, JM Kuner, R Behrens, J Offermanns, S Neuron 35:51-63 inferred by electronic annotation IEA GO IEA 3.6.5.4 3.6.5.3 3.6.5.2 3.6.5.1 G alpha (12/13) auto-inactivates by hydrolysing GTP to GDP G alpha (12/13) auto-inactivates by hydrolysing GTP to GDP This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10602549 1 Converted from EntitySet in Reactome Reactome DB_ID: 10603273 1 G-protein alpha (12/13):GDP [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10602549 GO 0003924 GO molecular function Reactome Database ID Release 83 10603274 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603274 Reactome Database ID Release 83 10603276 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10603276 Reactome R-GGA-418574 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-418574.1 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). 7937899 Pubmed 1994 Mechanism of GTP hydrolysis by G-protein alpha subunits Kleuss, C Raw, AS Lee, E Sprang, SR Gilman, AG Proc Natl Acad Sci U S A 91:9828-31 inferred by electronic annotation IEA GO IEA Inactive G alpha (12/13) reassociates with G beta:gamma Inactive G alpha (12/13) reassociates with G beta:gamma This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10603273 1 Reactome DB_ID: 10584699 2 Converted from EntitySet in Reactome Reactome DB_ID: 10585153 1 Reactome Database ID Release 83 10608561 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10608561 Reactome R-GGA-751039 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-751039.1 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. 16923326 Pubmed 2006 Structural basis of function in heterotrimeric G proteins Oldham, WM Hamm, HE Q Rev Biophys 39:117-66 inferred by electronic annotation IEA GO IEA G alpha (12) binds BTK G alpha (12) binds BTK This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10585157 1 G-protein alpha (12):GTP [plasma membrane] G-protein alpha (12):GTP Reactome DB_ID: 10585143 1 UniProt:A0A3Q2U2K8 UniProt A0A3Q2U2K8 1 EQUAL 381 EQUAL Reactome DB_ID: 29438 1 Reactome Database ID Release 83 10585157 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10585157 Reactome R-GGA-114525 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-114525.1 Reactome DB_ID: 10626696 1 UniProt:A0A1D5NXK5 UniProt A0A1D5NXK5 2 EQUAL 659 EQUAL Reactome DB_ID: 10659841 1 G alpha (12):BTK [plasma membrane] G alpha (12):BTK Reactome DB_ID: 10585157 1 Reactome DB_ID: 10626696 1 2 EQUAL 659 EQUAL Reactome Database ID Release 83 10659841 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10659841 Reactome R-GGA-8964310 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8964310.1 Reactome Database ID Release 83 10659847 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10659847 Reactome R-GGA-8964274 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8964274.1 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. 9796816 Pubmed 1998 The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain Jiang, Y Ma, W Wan, Y Kozasa, T Hattori, S Huang, X Y Nature 395:808-13 inferred by electronic annotation IEA GO IEA BTK in G alpha (12)-BTK complex is activated BTK in G alpha (12)-BTK complex is activated This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10659841 1 Reactome DB_ID: 10659841 1 Reactome Database ID Release 83 10659843 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10659843 Reactome R-GGA-8964246 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8964246.1 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. 11742120 Pubmed 2002 Competing modes of self-association in the regulatory domains of Bruton's tyrosine kinase: intramolecular contact versus asymmetric homodimerization Laederach, Alain Cradic, Kendall W Brazin, Kristine N Zamoon, Jamillah Fulton, D Bruce Huang, Xin-Yun Andreotti, Amy H Protein Sci. 11:36-45 inferred by electronic annotation IEA GO IEA G alpha (12)-BTK complex dissociates to Active BTK and G alpha (12) G alpha (12)-BTK complex dissociates to Active BTK and G alpha (12) This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10659841 1 Reactome DB_ID: 10585157 1 Reactome DB_ID: 10626696 1 2 EQUAL 659 EQUAL Reactome Database ID Release 83 10659859 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10659859 Reactome R-GGA-8964333 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8964333.1 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. inferred by electronic annotation IEA GO IEA Reactome Database ID Release 83 10669081 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10669081 Reactome R-GGA-416482 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-416482.1 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. 16102047 Pubmed 2005 Protease-activated receptors in hemostasis, thrombosis and vascular biology Coughlin, SR J Thromb Haemost 3:1800-14 12588974 Pubmed 2003 Inhibitory and stimulatory regulation of Rac and cell motility by the G12/13-Rho and Gi pathways integrated downstream of a single G protein-coupled sphingosine-1-phosphate receptor isoform Sugimoto, N Takuwa, N Okamoto, H Sakurada, S Takuwa, Y Mol Cell Biol 23:1534-45 18814923 Pubmed 2008 G(12)/G(13)-mediated signalling in mammalian physiology and disease Worzfeld, T Wettschureck, N Offermanns, S Trends Pharmacol Sci 29:582-9 7559569 Pubmed 1995 G alpha 12 and G alpha 13 stimulate Rho-dependent stress fiber formation and focal adhesion assembly Buhl, AM Johnson, NL Dhanasekaran, N Johnson, GL J Biol Chem 270:24631-4 inferred by electronic annotation IEA GO IEA