BioPAX pathway converted from "Autophosphorylation of KIT" in the Reactome database. 2.7.10.2 Autophosphorylation of KIT Autophosphorylation of KIT 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: 10588428 1 plasma membrane GO 0005886 KIT:sSCF dimer:KIT [plasma membrane] KIT:sSCF dimer:KIT Reactome DB_ID: 10588418 2 UniProt:Q08156 Reactome http://www.reactome.org Gallus gallus NCBI Taxonomy 9031 UniProt Q08156 Chain Coordinates 26 EQUAL 976 EQUAL Reactome DB_ID: 10588424 1 extracellular region GO 0005576 sSCF dimer [extracellular region] sSCF dimer Reactome DB_ID: 10588422 2 UniProt:Q09108 KITLG UniProt Q09108 26 EQUAL 190 EQUAL Reactome Database ID Release 82 10588424 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=10588424 Reactome R-GGA-1433307 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-1433307.1 Reactome Database ID Release 82 10588428 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=10588428 Reactome R-GGA-205208 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-205208.1 Reactome DB_ID: 113592 14 cytosol GO 0005829 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 29370 14 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 Reactome DB_ID: 10588454 1 p-7Y-KIT:sSCF dimer:p-7Y-KIT [plasma membrane] p-7Y-KIT:sSCF dimer:p-7Y-KIT Reactome DB_ID: 10588452 2 O4'-phospho-L-tyrosine at 568 (in Homo sapiens) 568 EQUAL O4'-phospho-L-tyrosine [MOD:00048] O4'-phospho-L-tyrosine at 570 (in Homo sapiens) 570 EQUAL O4'-phospho-L-tyrosine at 703 (in Homo sapiens) 703 EQUAL O4'-phospho-L-tyrosine at 721 (in Homo sapiens) 721 EQUAL O4'-phospho-L-tyrosine at 730 (in Homo sapiens) 730 EQUAL O4'-phospho-L-tyrosine at 823 (in Homo sapiens) 823 EQUAL O4'-phospho-L-tyrosine at 936 (in Homo sapiens) 936 EQUAL 26 EQUAL 976 EQUAL Reactome DB_ID: 10588424 1 Reactome Database ID Release 82 10588454 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=10588454 Reactome R-GGA-205310 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-205310.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10588428 GO 0004713 GO molecular function Reactome Database ID Release 82 10588491 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=10588491 Reactome Database ID Release 82 10588505 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=10588505 Reactome R-GGA-205289 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-205289.1 The cytoplasmic domain of KIT contains a bipartite kinase domain separated by 77 residues. The first part of the catalytic domain contains the ATP binding region while the second part contains an activation loop. Both parts of the domain have a number of possible autophosphorylation sites. In contrast to many other tyrosine kinases, autophosphorylation of the activation loop does not seem to be involved in the activation of the kinase activity nor it is required for full kinase activity (DiNitto et al. 2010). Instead, phosphorylation sites in the juxtamembrane region are important for activation of the kinase activity. The dimerized KIT acts as both enzyme and substrate for itself and autophosphorylates these specific tyrosine residues with in the kinases domains in trans as well as tyrosine residues outside the kinase domain. The resulting phosphotyrosine residues serve as docking sites for a number of signal transduction molecules containing Src-homology 2 (SH2) and phosphotyrosine-binding (PTB) domains. A majority of the autophosphorylation sites reside outside the kinase domain. 20147452 Pubmed 2010 Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance DiNitto, JP Deshmukh, GD Zhang, Y Jacques, SL Coli, R Worrall, JW Diehl, W English, JM Wu, JC J Biochem 147:601-9 16129412 Pubmed 2005 Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor Roskoski, Robert Jr Biochem Biophys Res Commun 337:1-13 7509796 Pubmed 1994 Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells Serve, H Hsu, YC Besmer, P J Biol Chem 269:6026-30 12824176 Pubmed 2003 Structure of a c-kit product complex reveals the basis for kinase transactivation Mol, CD Lim, KB Sridhar, V Zou, H Chien, EY Sang, BC Nowakowski, J Kassel, DB Cronin, CN McRee, DE J Biol Chem 278:31461-4 9038210 Pubmed 1997 Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes Price, DJ Rivnay, B Fu, Y Jiang, S Avraham, S Avraham, H J Biol Chem 272:5915-20 10377264 Pubmed 1999 Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor Thömmes, K Lennartsson, J Carlberg, M Rönnstrand, Lars Biochem J 341:211-6 inferred by electronic annotation IEA GO IEA INHIBITION Reactome Database ID Release 82 10588508 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=10588508 Reactome DB_ID: 10588501 KIT:sSCF dimer:KIT:type I KIT binding TKIs: [plasma membrane] KIT:sSCF dimer:KIT:type I KIT binding TKIs: Reactome DB_ID: 10588428 1 Converted from EntitySet in Reactome Reactome DB_ID: 9669710 1 type I KIT binding TKIs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dovitinib [cytosol] midostaurin [cytosol] avapritinib [cytosol] Guide to Pharmacology 5962 Guide to Pharmacology 5702 Guide to Pharmacology 10368 Reactome Database ID Release 82 10588501 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=10588501 Reactome R-GGA-9669711 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-9669711.1 INHIBITION Reactome Database ID Release 82 10588507 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=10588507 Reactome DB_ID: 10588499 KIT:type II TKIs [plasma membrane] KIT:type II TKIs Reactome DB_ID: 10588418 1 26 EQUAL 976 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 9669722 1 type II KIT binding TKIs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity sorafenib [cytosol] dasatinib [cytosol] masitinib [cytosol] axitinib [cytosol] sunitinib [cytosol] regorafenib [cytosol] imatinib [cytosol] ponatinib [cytosol] nilotinib [cytosol] cabozantinib [cytosol] lenvatinib [cytosol] Guide to Pharmacology 5711 Guide to Pharmacology 5678 Guide to Pharmacology 5656 Guide to Pharmacology 5659 Guide to Pharmacology 5713 Guide to Pharmacology 5891 Guide to Pharmacology 5687 Guide to Pharmacology 5890 Guide to Pharmacology 5697 Guide to Pharmacology 5887 Guide to Pharmacology 7426 Reactome Database ID Release 82 10588499 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=10588499 Reactome R-GGA-9669721 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-9669721.1 INHIBITION Reactome Database ID Release 82 10588509 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=10588509 Reactome DB_ID: 10588503 KIT:ripretinib [plasma membrane] KIT:ripretinib Reactome DB_ID: 9674322 1 ripretinib [Guide to Pharmacology:9175] ripretinib DCC-2618 DCC2618 Guide to Pharmacology 9175 Reactome DB_ID: 10588418 1 26 EQUAL 976 EQUAL Reactome Database ID Release 82 10588503 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=10588503 Reactome R-GGA-9681373 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-9681373.1 INHIBITION Reactome Database ID Release 82 10588506 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=10588506 Reactome DB_ID: 10588497 p-KIT (S741,746):PKC alpha [plasma membrane] p-KIT (S741,746):PKC alpha Reactome DB_ID: 10588495 1 O-phospho-L-serine at 741 (in Homo sapiens) 741 EQUAL O-phospho-L-serine [MOD:00046] O-phospho-L-serine at 746 (in Homo sapiens) 746 EQUAL 26 EQUAL 976 EQUAL Reactome DB_ID: 10576829 1 UniProt:R4GHL2 UniProt R4GHL2 2 EQUAL 672 EQUAL Reactome Database ID Release 82 10588497 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=10588497 Reactome R-GGA-1433473 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-1433473.1