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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Activation of Rap1 by cytosolic GEFs Activation of Rap1 by cytosolic GEFs This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29438 1 cytosol 去 0005829 GTP [ChEBI:15996] GTP Guanosine 5'-triphosphate Reactome //www.joaskin.com ChEBI 15996 Reactome DB_ID: 10130089 1 plasma membrane 去 0005886 RAP1:GDP [plasma membrane] RAP1:GDP Converted from EntitySet in Reactome Reactome DB_ID: 10130057 1 RAP1 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity RAP1B [plasma membrane] RAP1A [plasma membrane] Sus scrofa NCBI Taxonomy 9823 UniProt A0A286ZVJ2 UniProt F2Z5K3 Reactome DB_ID: 29420 1 GDP [ChEBI:17552] GDP Guanosine 5'-diphosphate Guanosine diphosphate ChEBI 17552 Reactome Database ID Release 77 10130089 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130089 Reactome R-SSC-354074 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354074.1 Reactome DB_ID: 10130059 1 RAP1:GTP [plasma membrane] RAP1:GTP Converted from EntitySet in Reactome Reactome DB_ID: 10130057 1 Reactome DB_ID: 29438 1 Reactome Database ID Release 77 10130059 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130059 Reactome R-SSC-354126 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354126.1 Reactome DB_ID: 29420 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10130101 CalDAG-GEFs:DAG:Ca2+ [plasma membrane] CalDAG-GEFs:DAG:Ca2+ Reactome DB_ID: 114519 1 1,2-diacyl-sn-glycerol [ChEBI:17815] 1,2-diacyl-sn-glycerol ChEBI 17815 Reactome DB_ID: 74016 1 calcium(2+) [ChEBI:29108] calcium(2+) ChEBI 29108 Converted from EntitySet in Reactome Reactome DB_ID: 10130099 1 CalDAG-GEFs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity RASGRP1 [cytosol] RASGRP2 [cytosol] UniProt F1SS17 UniProt A0A287AFQ0 Reactome Database ID Release 77 10130101 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130101 Reactome R-SSC-392841 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-392841.1 去 0005085 去molecular function Reactome Database ID Release 77 10130102 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130102 Reactome Database ID Release 77 10130104 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130104 Reactome R-SSC-354173 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354173.1 Signals from agonist receptors (such as GPVI) trigger the production of PIP3, DAG, cAMP and elevated Ca++ levels. This leads to the activation and translocation of active Rap1-GTP to the plasma membrane. Rap-GEFs stimulate the replacement of GDP for GTP, activating Rap1. Several Rap1 GEFs have been identified enabling Rap1 to respond to diverse stimuli. CalDAG-GEFs activate Rap1 in response to calcium and DAG, downstream of Phospholipase C. EPAC (exchange proteins directly activated by cAMP) GEFs are activated by binding cAMP. 15334074 Pubmed 2004 CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation Crittenden, JR Bergmeier, W Zhang, Y Piffath, CL Liang, Y Wagner, DD 所,德 Graybiel, AM Nat地中海10:982-6 15469846 Pubmed 2004 RIAM、Ena / VASP和Profilin配体相互作用ith Rap1-GTP and mediates Rap1-induced adhesion Lafuente, EM van Puijenbroek, AA Krause, M Carman, CV Freeman, GJ Berezovskaya, A Constantine, E Springer, TA Gertler, FB Boussiotis, VA Dev Cell 7:585-95 12585966 Pubmed 2003 Bidirectional integrin alphaIIbbeta3 signalling regulating platelet adhesion under flow: contribution of protein kinase C Giuliano, S Nesbitt, WS Rooney, M 杰克逊,SP Biochem J 372:163-72 16757337 Pubmed 2006 Rap1 regulation of RIAM and cell adhesion Lafuente, E Boussiotis, VA Methods Enzymol 407:345-58 16076873 Pubmed 2005 Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions Stork, PJ Dillon, TJ Blood 106:2952-61 inferred by electronic annotation IEA 去 IEA Activation of Rap1 by membrane-associated GEFs Activation of Rap1 by membrane-associated GEFs This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29438 1 Reactome DB_ID: 10130089 1 Reactome DB_ID: 10130059 1 Reactome DB_ID: 29420 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10136546 Rap1 cAMP-GEFs [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity RAPGEF3 [plasma membrane] RAPGEF4 [plasma membrane] UniProt I3L7Z0 UniProt F1S067 Reactome Database ID Release 77 10144939 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10144939 Reactome Database ID Release 77 10144941 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10144941 Reactome R-SSC-939265 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-939265.1 Signals from agonist receptors (such as GPVI) trigger the production of PIP3, DAG, cAMP and elevated Ca++ levels. This leads to the activation and translocation of active Rap1-GTP to the plasma membrane. Rap-GEFs stimulate the replacement of GDP for GTP, activating Rap1. Several Rap1 GEFs have been identified enabling Rap1 to respond to diverse stimuli. CalDAG-GEFs activate Rap1 in response to calcium and DAG, downstream of Phospholipase C. EPAC (exchange proteins directly activated by cAMP) GEFs are activated by binding cAMP. inferred by electronic annotation IEA 去 IEA Translocation of RIAM to plasma membrane Translocation of RIAM to plasma membrane This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10130059 1 Reactome DB_ID: 10130063 1 UniProt:A0A286ZVU8 APBB1IP UniProt A0A286ZVU8 Chain Coordinates 1 平等的 666 平等的 Reactome DB_ID: 179856 1 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [ChEBI:18348] 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate PIP2 ChEBI 18348 Reactome DB_ID: 10130065 1 Rap1-GTP:PIP2:RIAM [plasma membrane] Rap1-GTP:PIP2:RIAM Reactome DB_ID: 10130059 1 Reactome DB_ID: 10130063 1 1 平等的 666 平等的 Reactome DB_ID: 179856 1 Reactome Database ID Release 77 10130065 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130065 Reactome R-SSC-354110 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354110.1 Reactome Database ID Release 77 10130067 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130067 Reactome R-SSC-354060 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354060.1 Upon the production of activated Rap1A at the plasma membrane, RIAM interacts with Rap1A-GTP with its N-ter RA domain, and with its C-ter PH domain it interacts with PIP2. 17624957 Pubmed 2007 Platelet integrins and immunoreceptors Kasirer-Friede, A Kahn, ML Shattil, Sanford J Immunol Rev 218:247-64 18434644 Pubmed 2008 Talin at a glance Critchley, DR Gingras, AR J Cell Sci 121:1345-7 inferred by electronic annotation IEA 去 IEA Activation of Talin Activation of Talin This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10130065 1 Reactome DB_ID: 10130071 1 UniProt:A0A287AC34 TLN1 UniProt A0A287AC34 1 平等的 2541 平等的 Reactome DB_ID: 10130073 1 蛋白:RIAM复杂[等离子断片ne] Talin:RIAM complex Reactome DB_ID: 10130065 1 Reactome DB_ID: 10130071 1 1 平等的 2541 平等的 Reactome Database ID Release 77 10130073 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130073 Reactome R-SSC-354176 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354176.1 Reactome Database ID Release 77 10130087 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130087 Reactome r - ssc - 354097 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354097.1 Talin is one of the major cytoskeletal proteins involved in integrin activation and linking the resulting focal adhesion (FA) with cytoskeleton. Talin comprises an N-ter head region and a flexible rod domain. The head region has the FERM domain (subdivided into F1, F2 and F3 subdomains), which has the binding sites for beta integrin cytoplasmic regions and actin binding sites close to the C-terminal rod domain.
Talin exists in closed inactive conformation, where the head region interacts with the rod domain masking the integrin binding sites. At the plasma membrane the RIAM bound to active Rap1 recruits talin to form the integrin activation complex. This interaction exposes the integrin-binding site in talin F3 domain leading to integrin activation.
16102045 Pubmed 2005 Integrin activation by talin Ratnikov, BI Partridge, AW Ginsberg, MH J Thromb Haemost 3:1783-90 inferred by electronic annotation IEA 去 IEA Integrin alphaIIb beta3 activation Integrin alphaIIb beta3 activation This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10130081 1 整合素alphaIIb beta3: p-Y530-SRC:埋头[等离子membrane] Integrin alphaIIb beta3:p-Y530-SRC:CSK Reactome DB_ID: 10130079 1 p-Y530-SRC:CSK [cytosol] p-Y530-SRC:CSK Reactome DB_ID: 10126749 1 UniProt:F1SJ27 CSK UniProt F1SJ27 1 平等的 450 平等的 Reactome DB_ID: 10122533 1 UniProt:K7GPR7 SRC UniProt K7GPR7 O4'-phospho-L-tyrosine at 530 (in Homo sapiens) 530 平等的 O4'-phospho-L-tyrosine [MOD:00048] N-myristoylglycine at 2 (in Homo sapiens) 2 平等的 N-myristoylglycine [MOD:00068] 2 平等的 536 平等的 Reactome Database ID Release 77 10130079 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130079 Reactome R-SSC-377606 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-377606.1 Reactome DB_ID: 10130077 1 Integrin alpha2bbeta3 [plasma membrane] Integrin alpha2bbeta3 Reactome DB_ID: 10128513 1 UniProt:A0A5G2R7K7 ITGB3 UniProt A0A5G2R7K7 27 平等的 788 平等的 Reactome DB_ID: 10130075 1 Ghost homologue of ITGA2B(32-1039) [plasma membrane] Ghost homologue of ITGA2B(32-1039) Reactome Database ID Release 77 10130077 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130077 Reactome R-SSC-114514 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-114514.1 Reactome Database ID Release 77 10130081 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130081 Reactome R-SSC-377608 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-377608.1 Reactome DB_ID: 10130073 1 Reactome DB_ID: 10130083 1 Integrin alphaIIb beta3:p-Y530-SRC:CSK:Talin:RIAM complex [plasma membrane] Integrin alphaIIb beta3:p-Y530-SRC:CSK:Talin:RIAM complex Reactome DB_ID: 10130081 1 Reactome DB_ID: 10130073 1 Reactome Database ID Release 77 10130083 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130083 Reactome R-SSC-354130 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354130.1 Reactome Database ID Release 77 10130085 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10130085 Reactome R-SSC-354077 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354077.1 The interaction between talin and integrin alphaIIb beta3 breaks the putative salt bridge between the alphaIIb (R995) and beta3 (D723) integrin chains and induces conformational changes in their external domains increasing their affinity for fibrinogen and other ECM ligands. Breaking of this salt bridge is necessary but not sufficient for full activation.
The Talin F3 subdomain of the FERM domain has a phosphotyrosine binding (PTB) domain fold. This domain interacts with the membrane-proximal (MP) region within the integrin beta3 chain. The primary function of this interaction is to provide an initial strong linkage between talin and integrin and this interaction holds the key to the molecular recognition required for activation. In platelets SRC kinase and its negative regulator CSK associates constitutively with integrin alphaIIbbeta3. SRC is involved in alphaIIbbeta3 dependent activation of SYK, and both SRC and SYK are required to initiate cytoskeletal events responsible for platelet spreading on fibrinogen. 14754902 Pubmed 2004 Integrin activation Calderwood, DA J Cell Sci 117:657-66 11940607 Pubmed 2002 Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton Obergfell, A Eto, K Mocsai, A Buensuceso, C Moores, SL Brugge, JS Lowell, CA Shattil, Sanford J J Cell Biol 157:265-75 10446041 Pubmed 1999 Integrin signaling Giancotti, FG Ruoslahti, E Science 285:1028-32 17218263 Pubmed 2007 Structural basis of integrin activation by talin Wegener, KL Partridge, AW Han, J Pickford, AR Liddington, RC Ginsberg, MH Campbell, ID Cell 128:171-82 inferred by electronic annotation IEA 去 IEA Activated integrin alphaIIb beta3 binds SHC1 Activated integrin alphaIIb beta3 binds SHC1 This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10130083 1 Reactome DB_ID: 10114759 1 UniProt:A0A5K1V5Y3 SHC1 UniProt A0A5K1V5Y3 1 平等的 583 平等的 Reactome DB_ID: 10139666 1 Integrin alphaIIb beta 3:p(Y530)-SRC:CSK:Talin:RIAM complex:SHC [plasma membrane] Integrin alphaIIb beta 3:p(Y530)-SRC:CSK:Talin:RIAM complex:SHC Reactome DB_ID: 10130083 1 Reactome DB_ID: 10114759 1 1 平等的 583 平等的 Reactome Database ID Release 77 10139666 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10139666 Reactome R-SSC-432098 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-432098.1 Reactome Database ID Release 77 10139668 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10139668 Reactome R-SSC-432096 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-432096.1 The beta 3 integrin cytoplasmic tail binds SH2-containing protein (SHC), an adapter in Ras signaling. Phosphorylation of Y785 may be necessary for binding; phosphorylation of T779 inhibits SHC binding. Mice expressing a mutated beta 3 where Y773 and Y785 have been mutated to F exhibit rebleeding from tail wounds and subtle defects in clot retraction and platelet aggregation. 10548108 Pubmed 1999 Integrin cytoplasmic tyrosine motif is required for outside-in alphaIIbbeta3 signalling and platelet function Law, DA DeGuzman, FR Heiser, P Ministri-Madrid, K Killeen, N Phillips, DR Nature 401:808-11 10964917 Pubmed 2000 Identification of shc as the primary protein binding to the tyrosine-phosphorylated beta 3 subunit of alpha IIbbeta 3 during outside-in integrin platelet signaling Cowan, KJ Law, DA Phillips, DR J Biol Chem 275:36423-9 8631894 Pubmed 1996 Outside-in integrin signal transduction. Alpha IIb beta 3-(GP IIb IIIa) tyrosine phosphorylation induced by platelet aggregation Law, DA Nannizzi-Alaimo, L Phillips, DR J Biol Chem 271:10811-5 inferred by electronic annotation IEA 去 IEA SHC1 bound to integrin alphaIIb beta3 is phosphorylated somehow SHC1 bound to integrin alphaIIb beta3 is phosphorylated somehow This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10139666 1 Reactome DB_ID: 10140287 1 Integrin alpha IIb beta 3:p-Y530-SRC:CSK:Talin:RIAM complex:p-Y427-SHC [plasma membrane] Integrin alpha IIb beta 3:p-Y530-SRC:CSK:Talin:RIAM complex:p-Y427-SHC Reactome DB_ID: 10130083 1 Reactome DB_ID: 10114747 1 O4'-phospho-L-tyrosine at 427 (in Homo sapiens) 427 平等的 1 平等的 583 平等的 Reactome Database ID Release 77 10140287 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10140287 Reactome R-SSC-443900 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-443900.1 Reactome Database ID Release 77 10140289 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10140289 Reactome R-SSC-443905 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-443905.1 In a mechanism that is presumed to be analagous to signaling of SHC downstream of the insulin and TrkA receptors, SHC becomes phosphorylated and dissociates from the integrin alphaIIb beta3 complex. 8755247 Pubmed 1996 Not all Shc's roads lead to Ras Bonfini, L Migliaccio, E Pelicci, G Lanfrancone, L Pelicci, PG Trends Biochem Sci 21:257-61 inferred by electronic annotation IEA 去 IEA SHC1 dissociates from integrin alphaIIb beta3 SHC1 dissociates from integrin alphaIIb beta3 This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10140287 1 Reactome DB_ID: 10130083 1 Reactome DB_ID: 10114747 1 O4'-phospho-L-tyrosine at 427 (in Homo sapiens) 427 平等的 1 平等的 583 平等的 Reactome Database ID Release 77 10140291 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10140291 Reactome R-SSC-443910 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-443910.1 In a mechanism that is presumed to be analagous to signaling of SHC downstream of the insulin and TrkA receptors, SHC becomes phosphorylated and dissociates from the integrin alphaIIb beta3 complex. inferred by electronic annotation IEA 去 IEA Reactome Database ID Release 77 10203137 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10203137 Reactome R-SSC-354192 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-354192.1 Integrins are a major family of cell surface receptors that modulate cell adhesion, migration, proliferation and survival through interaction with the extracellular matrix (ECM) and the actin cytoskeleton. Integrins are type 1 transmembrane proteins that exist at the cell surface as heterodimers of alpha and beta subunits, of which there are 18 and 8 different isoforms, respectively, in human cells. In addition to their mechanical role in mediating contact between the ECM and the cytoskeleton, integrins also modulate intracellular signaling pathways governing cytoskeletal rearrangements and pro-survival and mitogenic signaling (reviewed in Hehlgans et al, 2007; Harburger and Calderwood, 2009; Ata and Antonescu, 2017).
In this pathway, we describe signaling through integrin alphaIIb beta3 as a representative example.
At the sites of vascular injury bioactive molecules such as thrombin, ADP, collagen, fibrinogen and thrombospondin are generated, secreted or exposed. These stimuli activate platelets, converting the major platelet integrin alphaIIbbeta3 from a resting state to an active conformation, in a process termed integrin priming or 'inside-out signalling'. Integrin activation refers to the change required to enhance ligand-binding activity. The activated alphaIIbbeta3 interacts with the fibrinogen and links platelets together in an aggregate to form a platelet plug. AlphaIIbbeta3 bound to fibrin generates more intracellular signals (outside-in signalling), causing further platelet activation and platelet-plug retraction.
In the resting state the alpha and beta tails are close together. This interaction keeps the membrane proximal regions in a bent conformation that maintains alphaIIbbeta3 in a low affinity state.
Integrin alphaIIbbeta3 is released from its inactive state by interaction with the protein talin. Talin interacts with the beta3 cytoplasmic domain and disrupts the salt bridge between the alpha and beta chains. This separation in the cytoplasmic regions triggers the conformational change in the extracellular domain that increases its affinity to fibrinogen.
Much of talin exists in an inactive cytosolic pool, and the Rap1 interacting adaptor molecule (RIAM) is implicated in talin activation and translocation to beta3 integrin cytoplasmic domain.
19118207 Pubmed 2009 Integrin signalling at a glance Harburger, David S Calderwood, David A J. Cell. Sci. 122:159-63 10605720 Pubmed 1999 Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways Shattil, Sanford J Thromb Haemost 82:318-25 15205259 Pubmed 2004 Integrins: dynamic scaffolds for adhesion and signaling in platelets Shattil, Sanford J Newman, PJ Blood 104:1606-15 17084981 Pubmed 2007 Signalling via integrins: implications for cell survival and anticancer strategies Hehlgans, S Haase, M Cordes, N Biochim Biophys Acta 1775:163-80 28106780 Pubmed 2017 Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer Ata, Rehman Antonescu, Costin N Int J Mol Sci 18: 16102042 Pubmed 2005 GPVI and integrin alphaIIb beta3 signaling in platelets Watson, SP Auger, JM McCarty, OJ Pearce, AC J Thromb Haemost 3:1752-62 10508650 Pubmed 1999 Integrin alpha(IIb)beta(3) signaling in platelet adhesion and aggregation Parise, LV Curr Opin Cell Biol 11:597-601 inferred by electronic annotation IEA 去 IEA