BioPAX pathway converted from "Autophosphorylation of KIT" in the Reactome database. LEFT-TO-RIGHT 2.7.10.2 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> KIT:sSCF dimer:KIT Reactome DB_ID: 10588428 plasma membrane GENE ONTOLOGY GO:0005886 KIT Q08156 Reactome DB_ID: 10588418 UniProt:Q08156 Gallus gallus NCBI Taxonomy 9031 UniProt Q08156 26 EQUAL 976 EQUAL Reactome Database ID Release 82 10588418 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=10588418 Reactome R-GGA-197662 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-197662.1 Reactome http://www.reactome.org 2 sSCF dimer Reactome DB_ID: 10588424 extracellular region GENE ONTOLOGY GO:0005576 KITLG KITLG-1(26-190) Q09108 Reactome DB_ID: 10588422 UniProt:Q09108 KITLG UniProt Q09108 26 EQUAL 190 EQUAL Reactome Database ID Release 82 10588422 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=10588422 Reactome R-GGA-708330 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-708330.1 2 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 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 ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 cytosol GENE ONTOLOGY GO:0005829 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 82 113592 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=113592 Reactome R-ALL-113592 5 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-ALL-113592.5 COMPOUND C00002 additional information MI MI:0361 14 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 29370 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 82 29370 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=29370 Reactome R-ALL-29370 5 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-ALL-29370.5 COMPOUND C00008 14 p-7Y-KIT:sSCF dimer:p-7Y-KIT Reactome DB_ID: 10588454 Q08156 phospho-p-7Y-KIT Reactome DB_ID: 10588452 568 EQUAL O4'-phospho-L-tyrosine MOD MOD:00048 570 EQUAL 703 EQUAL 721 EQUAL 730 EQUAL 823 EQUAL 936 EQUAL 26 EQUAL 976 EQUAL Reactome Database ID Release 82 10588452 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=10588452 Reactome R-GGA-205207 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-205207.1 2 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 ACTIVATION GENE ONTOLOGY GO:0004713 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity 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 from electronic annotation EVIDENCE CODE ECO:0000203 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 KIT:sSCF dimer:KIT:type I KIT binding TKIs: Reactome DB_ID: 10588501 1 Converted from EntitySet in Reactome type I KIT binding TKIs Reactome DB_ID: 9669710 TKI258 dovitinib Reactome DB_ID: 1839035 dovitinib [Guide to Pharmacology:5962] dovitinib Chir 258 CHIR-258 TKI 258 TKI-258 Guide to Pharmacology 5962 Reactome Database ID Release 82 1839035 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=1839035 Reactome R-ALL-1839035 3 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-ALL-1839035.3 PubChem Compound 9886808 PKC412 midostaurin Reactome DB_ID: 2038921 midostaurin [Guide to Pharmacology:5702] midostaurin CGP 41231 CGP 41251 N-benzoylstaurosporine PKC412 Rydapt&reg; Guide to Pharmacology 5702 Reactome Database ID Release 82 2038921 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=2038921 Reactome R-ALL-2038921 3 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-ALL-2038921.3 ChEBI 63452 BLU285 avapritinib BLU-285 Reactome DB_ID: 9671491 avapritinib [Guide to Pharmacology:10368] avapritinib BLU285 BLU-285 Guide to Pharmacology 10368 Reactome Database ID Release 82 9671491 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=9671491 Reactome R-ALL-9671491 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-ALL-9671491.1 Reactome Database ID Release 82 9669710 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=9669710 Reactome R-ALL-9669710 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-ALL-9669710.1 1 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 KIT:type II TKIs Reactome DB_ID: 10588499 1 Converted from EntitySet in Reactome type II KIT binding TKIs Reactome DB_ID: 9669722 imatinib Reactome DB_ID: 9659761 imatinib [Guide to Pharmacology:5687] imatinib CGP 57148 Gleevec&reg; Glivec&reg; STI571 Guide to Pharmacology 5687 Reactome Database ID Release 82 9659761 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=9659761 Reactome R-ALL-9659761 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-ALL-9659761.1 Sutent sunitinib SU11248 Reactome DB_ID: 9669720 sunitinib [Guide to Pharmacology:5713] sunitinib SU11248 Sutent&reg; Guide to Pharmacology 5713 Reactome Database ID Release 82 9669720 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=9669720 Reactome R-ALL-9669720 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-ALL-9669720.1 regorafenib Reactome DB_ID: 9657514 regorafenib [Guide to Pharmacology:5891] regorafenib BAY 73-4506 Stivarga&reg; Guide to Pharmacology 5891 Reactome Database ID Release 82 9657514 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=9657514 Reactome R-ALL-9657514 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-ALL-9657514.1 ChEBI 68647 sorafenib Reactome DB_ID: 9657029 sorafenib [Guide to Pharmacology:5711] sorafenib BAY 43-9006 Nexavar Guide to Pharmacology 5711 Reactome Database ID Release 82 9657029 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=9657029 Reactome R-ALL-9657029 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-ALL-9657029.1 ChEBI 50924 AMN107 nilotinib AMN 107 Tasigna Reactome DB_ID: 9669716 nilotinib [Guide to Pharmacology:5697] nilotinib AMN107 AMN 107 Tasigna&reg; Guide to Pharmacology 5697 Reactome Database ID Release 82 9669716 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=9669716 Reactome R-ALL-9669716 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-ALL-9669716.1 AP24534 ponatinib Iclusig Reactome DB_ID: 9669717 ponatinib [Guide to Pharmacology:5890] ponatinib AP24534 Iclusig&reg; Guide to Pharmacology 5890 Reactome Database ID Release 82 9669717 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=9669717 Reactome R-ALL-9669717 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-ALL-9669717.1 AB1010 masitinib Reactome DB_ID: 2077524 masitinib [Guide to Pharmacology:5656] masitinib AB1010 AB-1010 Masican&reg; (proposed trade name) Guide to Pharmacology 5656 Reactome Database ID Release 82 2077524 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=2077524 Reactome R-ALL-2077524 3 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-ALL-2077524.3 ChEBI 63450 dasatinib BMS 345825 BMS 354825 BMS 35482513 Sprycel&reg; Reactome DB_ID: 9669723 dasatinib [Guide to Pharmacology:5678] dasatinib BMS 345825 BMS 354825 BMS 35482513 Sprycel&reg; Guide to Pharmacology 5678 Reactome Database ID Release 82 9669723 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=9669723 Reactome R-ALL-9669723 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-ALL-9669723.1 XL184 cabozantinib BMS907351 Cabometyx Cometriq XL-184 Reactome DB_ID: 9669718 cabozantinib [Guide to Pharmacology:5887] cabozantinib BMS907351 Cabometyx&reg; Cometriq&reg; XL184 XL-184 Guide to Pharmacology 5887 Reactome Database ID Release 82 9669718 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=9669718 Reactome R-ALL-9669718 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-ALL-9669718.1 Inlyta® axitinib AG 013736 AG-013736 AG013736 Reactome DB_ID: 9669719 axitinib [Guide to Pharmacology:5659] axitinib AG013736 AG 013736 AG-013736 Inlyta&reg; Guide to Pharmacology 5659 Reactome Database ID Release 82 9669719 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=9669719 Reactome R-ALL-9669719 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-ALL-9669719.1 E7080 lenvatinib Reactome DB_ID: 2023393 lenvatinib [Guide to Pharmacology:7426] lenvatinib E 7080 ER-203492-00 Kisplyx&reg; Lenvima&reg; Guide to Pharmacology 7426 Reactome Database ID Release 82 2023393 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=2023393 Reactome R-ALL-2023393 3 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-ALL-2023393.3 ChEBI 85994 Reactome Database ID Release 82 9669722 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=9669722 Reactome R-ALL-9669722 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-ALL-9669722.1 1 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 KIT:ripretinib Reactome DB_ID: 10588503 DCC2618 ripretinib DCC-2618 Reactome DB_ID: 9674322 ripretinib [Guide to Pharmacology:9175] ripretinib DCC2618 DCC-2618 Guide to Pharmacology 9175 Reactome Database ID Release 82 9674322 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=9674322 Reactome R-ALL-9674322 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-ALL-9674322.1 1 1 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 p-KIT (S741,746):PKC alpha Reactome DB_ID: 10588497 Q08156 phospho-p-S741,S746-KIT Reactome DB_ID: 10588495 741 EQUAL O-phospho-L-serine MOD MOD:00046 746 EQUAL 26 EQUAL 976 EQUAL Reactome Database ID Release 82 10588495 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=10588495 Reactome R-GGA-1433492 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-1433492.1 1 PRKCA R4GHL2 Reactome DB_ID: 10576829 UniProt:R4GHL2 UniProt R4GHL2 2 EQUAL 672 EQUAL Reactome Database ID Release 82 10576829 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=10576829 Reactome R-GGA-58196 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-58196.1 1 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