Signaling by SCF-KIT (Homo sapiens)

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3, 6, 8, 13, 38...15, 17, 37, 4929, 32, 629, 2145, 665, 193224, 25, 34, 60171, 4, 7, 16, 25...4, 25211131, 67692114, 22, 27, 35, 46336618, 22, 35, 43, 443251, 54, 59, 6622, 23, 4122, 27, 28, 36, 47...22, 26, 3512, 559, 10, 2113, 57, 6833, 5622, 48, 63, 68212, 3013, 20, 42, 6133Src family tyrosinekinases (SFKs)[cytosol]Src family tyrosinekinases (SFKs)[cytosol]sSCF dimer[extracellularregion]sSCF dimer[extracellularregion]p21 RAS [plasmamembrane]sSCF dimer[extracellularregion]Src family tyrosinekinases (SFKs)[cytosol]sSCF dimer[extracellularregion]p-KIT (S741,746):PKCalpha [plasmamembrane]Adapterproteins:p-KITcomplex [plasmamembrane]p-STATs [cytosol]sSCF dimer[extracellularregion]sSCF dimer[extracellularregion]p-STAT dimer[cytosol]sSCF dimer[extracellularregion]p-JAK2:SFKs:p-KITcomplex:p-STATdimers [plasmamembrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]sSCF dimer[extracellularregion]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p(Y)-GAB2:GRB2:p-SHP2:p-KITcomplex [plasmamembrane]sSCF dimer[extracellularregion]SHP-1:p-c-Kitcomplex [plasmamembrane]p-SHP2:p-KIT complex[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]SFKs:p-KIT complex[plasma membrane]Grb2:SOS:p-c-Kit/p-APS:p-c-Kitcomplex [plasmamembrane, cytosol,extracellularregion]SOCS1:p-KIT complex[plasma membrane]LNK:p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]nucleoplasmp-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]SFKs:p-KIT complex[plasma membrane]Adapter proteins[cytosol]Src family tyrosinekinases (SFKs)[cytosol]RAC1-GTP [cytosol]p-APS dimer:p-KITcomplex [plasmamembrane]GRB2:p-SHP2:p-KITcomplex [plasmamembrane]GRB2:SOS1 [cytosol]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]Src family tyrosinekinases (SFKs)[cytosol]KIT:sSCF dimer[plasma membrane]sSCF dimer[extracellularregion]sSCF dimer[extracellularregion]sSCF dimer[extracellularregion]GRB2:SOS1:p-KITcomplex [plasmamembrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]Grb2:SOS:p-c-Kit/p-APS:p-c-Kitcomplex [plasmamembrane, cytosol,extracellularregion]sSCF dimer[extracellularregion]p-APS dimer:p-KITcomplex [plasmamembrane]GRB2:SOS1 [cytosol]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p-STATs [cytosol]sSCF dimer[extracellularregion]Src family tyrosinekinases (SFKs)[cytosol]Tyrosinekinases:p-KITcomplex [plasmamembrane]p21 RAS [plasmamembrane]PTPRO:KIT [plasmamembrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]SFKs:p-KIT complex[plasma membrane]GRB2:SOS1 [cytosol]PI3K alpha [cytosol]SFKs:p-KIT complex[plasma membrane]GRB2:SOS1:p-KITcomplex [plasmamembrane]cytosolSOCS6:p-c-Kit:sSCFdimer:p-c-Kit[plasma membrane]SFKs:p-8Y-KIT:sSCFdimer:p-8Y-KIT[plasma membrane]Src family tyrosinekinases (SFKs)[cytosol]p-APS dimer:p-KITcomplex [plasmamembrane]sSCF dimer[extracellularregion]JAK2:SFKS:p-KITcomplex [plasmamembrane]APS dimer [cytosol]Tyrosine kinases[cytosol]Src family tyrosinekinases (SFKs)[cytosol]Src family tyrosinekinases (SFKs)[cytosol]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]APSdimer:p-c-Kit:SFKscomplex [plasmamembrane]PI3K alpha [cytosol]sSCF dimer[extracellularregion]sSCF dimer[extracellularregion]SFKs:p-KIT complex[plasma membrane]sSCF dimer[extracellularregion]SFKs:p-KIT complex[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]Src family tyrosinekinases (SFKs)[cytosol]p-APS dimer[cytosol]sSCF dimer[extracellularregion]p-SHP2:p-KIT complex[plasma membrane]sSCF dimer[extracellularregion]CBL:Grb2/p-APS:p-c-Kitcomplex [plasmamembrane]Src family tyrosinekinases (SFKs)[cytosol]SFKs:p-KIT complex[plasma membrane]Src family tyrosinekinases (SFKs)[cytosol]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p-SHP2:p-KIT complex[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]sSCF dimer[extracellularregion]SFKs:p-KIT complex[plasma membrane]KIT:sSCF dimer:KIT[plasma membrane]p-JAK2:SFKs:p-KITcomplex [plasmamembrane]GRB2:p-SHP2:p-KITcomplex [plasmamembrane]Src family tyrosinekinases (SFKs)[cytosol]p-SHP2:p-KIT complex[plasma membrane]p-JAK2:SFKs:p-KITcomplex:STATs[plasma membrane]p-JAK2:SFKs:p-KITcomplex:p-STATs[plasma membrane]sSCF dimer[extracellularregion]P13K:p(Y)-GAB2:GRB2:p-SHP2:p-KITcomplex [plasmamembrane]Src family tyrosinekinases (SFKs)[cytosol]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]APS dimer [cytosol]Src family tyrosinekinases (SFKs)[cytosol]SFKs:p-KIT complex[plasma membrane]sSCF dimer[extracellularregion]p-STATs[nucleoplasm]p-STAT dimers[nucleoplasm]p-APS dimer[cytosol]PI3K alpha [cytosol]p-SHP2:p-KIT complex[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]SFKs:p-KIT complex[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]p21 RAS:GDP [plasmamembrane]sSCF dimer[extracellularregion]Src family tyrosinekinases (SFKs)[cytosol]GAB2:GRB2:p-SHP2:p-KITcomplex [plasmamembrane]sSCF dimer[extracellularregion]SHP2:SFKs:p-KIT:sSCFdimer:p-KIT [plasmamembrane]sSCF dimer[extracellularregion]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]GRB2:SOS1 [cytosol]sSCF dimer[extracellularregion]SFKs:p-KIT complex[plasma membrane]p-8Y-KIT:sSCFdimer:p-8Y-KIT[plasma membrane]GRB2:SOS1:p-KITcomplex [plasmamembrane]SFKs:p-KIT complex[plasma membrane]Src family tyrosinekinases (SFKs)[cytosol]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]SFKs:p-KIT complex[plasma membrane]p21 RAS:GTP [plasmamembrane]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]SFKs:p-KIT complex[plasma membrane]sSCF dimer[extracellularregion]p-7Y-KIT:sSCFdimer:p-7Y-KIT[plasma membrane]RAC1-GDP [cytosol]GRB2:p-SHP2:p-KITcomplex [plasmamembrane]GRB2:p-SHP2:p-KITcomplex [plasmamembrane]SFKs:p-KIT complex[plasma membrane]p-VAV1:PIP3 [plasmamembrane]SFKs:p-KIT complex[plasma membrane]p-APS dimer[cytosol]STATs [cytosol]sSCF dimer[extracellularregion]PI3K:p-KIT:sSCFdimer:p-KIT [plasmamembrane]SRC-1 [cytosol]ADPp-7Y-KIT [plasmamembrane]p-Y629-SH2B2[cytosol]LCK [cytosol]CBL [cytosol]PTPN6SRC-1 [cytosol]YES1(2-543)[cytosol]SRC-1 [cytosol]FYN(2-537) [cytosol]p-Y-GAB2 [cytosol]SRC-1 [cytosol]KITLG-1(26-190)[extracellularregion]PTPN6 [cytosol]p-7Y-KIT [plasmamembrane]CBL:Grb2/p-APS:p-c-KitcomplexAPS dimerp-Y546,Y584-PTPN11[cytosol]KITLG-1(26-190)[extracellularregion]p-Y705-STAT3[nucleoplasm]LCK [cytosol]ATPKITLG-1(26-190)[extracellularregion]KITLG-1(26-190)[extracellularregion]LYN(2-512) [cytosol]LYN(2-512) [cytosol]GTPSRC-1 [cytosol]KITLG-1(26-190)[extracellularregion]p-Y694-STAT5A[cytosol]SOCS1SOCS6Tyrosine kinasesKITLG-1(26-190)[extracellularregion]p-KIT (S741,746):PKCalphaGRB2:p-SHP2:p-KITcomplexFYN(2-537) [cytosol]ADPLCK [cytosol]APSdimer:p-c-Kit:SFKscomplexKITYES1(2-543)[cytosol]Tyrosinekinases:p-KITcomplexp-STAT dimersSRC-1 [cytosol]FYN(2-537) [cytosol]p-7Y-KIT [plasmamembrane]GAB2 [cytosol]LYN(2-512) [cytosol]ATPSHP2:SFKs:p-KIT:sSCFdimer:p-KITKITLG-1(26-190)[extracellularregion]YES1(2-543)[cytosol]p-Y1007-JAK2[cytosol]KITLG-1(26-190)[extracellularregion]p-Y694-STAT5A[nucleoplasm]KIT [plasmamembrane]RAF/MAP kinasecascadep-JAK2:SFKs:p-KITcomplexKRAS(1-186) [plasmamembrane]p-8Y-KIT [plasmamembrane]LYN(2-512) [cytosol]YES1(2-543)[cytosol]p-Y629-SH2B2[cytosol]LCK [cytosol]p-7Y-KIT [plasmamembrane]PRKCASrc family tyrosinekinases (SFKs)JAK2:SFKS:p-KITcomplexLNK:p-7Y-KIT:sSCFdimer:p-7Y-KITKITLG-1(26-190)[extracellularregion]KITLG-1(26-190)[extracellularregion]p-Y546,Y584-PTPN11[cytosol]FYN(2-537) [cytosol]GRB2-1 [cytosol]GRB2-1 [cytosol]p-7Y-KIT [plasmamembrane]NRAS [plasmamembrane]p-Y546,Y584-PTPN11[cytosol]KITLG-1(26-190)[extracellularregion]GTP [cytosol]p-VAV1:PIP3FYN(2-537) [cytosol]GRB2-1 [cytosol]SRC-1 [cytosol]p-7Y-KIT [plasmamembrane]p-JAK2:SFKs:p-KITcomplex:STATsPIK3CA [cytosol]SOS1 [cytosol]GRB2-1 [cytosol]KITLG-1(26-190)[extracellularregion]p-7Y-KIT [plasmamembrane]KITLG-1(26-190)[extracellularregion]PI(3,4,5)P3LYN(2-512) [cytosol]YES1(2-543)[cytosol]JAK2 [cytosol]KITLG-1(26-190)[extracellularregion]GRB2:SOS1p-Y701-STAT1-1[cytosol]KITLG-1(26-190)[extracellularregion]p-7Y-KIT:sSCFdimer:p-7Y-KITLCK [cytosol]SFKs:p-KIT complexKITLG-1(26-190)[extracellularregion]KITLG-1(26-190)[extracellularregion]GRB2-1 [cytosol]GRAP [cytosol]p-7Y-KIT [plasmamembrane]p-7Y-KIT [plasmamembrane]ATPSRC-1 [cytosol]YES1(2-543)[cytosol]PIK3CA [cytosol]NRAS [plasmamembrane]GDP [cytosol]p-SHP2:p-KIT complexKITLG-1(26-190)[extracellularregion]p(Y)-GAB2:GRB2:p-SHP2:p-KITcomplexKIT [plasmamembrane]LCK [cytosol]KITLG-1(26-190)[extracellularregion]STAT1 [cytosol]SOCS1 [cytosol]p-Y699-STAT5B[nucleoplasm]PTPRO:KITFYN(2-537) [cytosol]KITLG-1(26-190)[extracellularregion]GTPATPp-APS dimer:p-KITcomplexSOS1 [cytosol]GAB2:GRB2:p-SHP2:p-KITcomplexP13K:p(Y)-GAB2:GRB2:p-SHP2:p-KITcomplexGRAP2 [cytosol]YES1(2-543)[cytosol]p-JAK2:SFKs:p-KITcomplex:p-STATdimersGDPFYN(2-537) [cytosol]SH2B2 [cytosol]p-Y699-STAT5B[cytosol]sSCF dimerCBLPRKCA [cytosol]LYN(2-512) [cytosol]STATsGrb2:SOS:p-c-Kit/p-APS:p-c-Kitcomplexp-7Y-KIT [plasmamembrane]KITLG-1(26-190)RAC1 [cytosol]SRC-1 [cytosol]SRC-1 [cytosol]LYN(2-512) [cytosol]LCK [cytosol]KITLG-1(26-190)[extracellularregion]KIT:sSCF dimer:KITFYN(2-537) [cytosol]p-Y1007-JAK2[cytosol]p-7Y-KIT [plasmamembrane]SH2B2 [cytosol]p-7Y-KIT [plasmamembrane]SRC-1 [cytosol]LYN(2-512) [cytosol]GDPFYN(2-537) [cytosol]p-Y701-STAT1-1[cytosol]LCK [cytosol]p-Y1007-JAK2[cytosol]LYN(2-512) [cytosol]YES1(2-543)[cytosol]KITLG-1(26-190)[extracellularregion]JAK2GTP [cytosol]SOCS6 [cytosol]p-7Y-KIT [plasmamembrane]GRB2-1 [cytosol]FYN(2-537) [cytosol]ADPKITLG-1(26-190)[extracellularregion]PTPN11p-7Y-KIT [plasmamembrane]ADPp-Y1007-JAK2[cytosol]SH2B3KITLG-1p-Y701-STAT1-1[nucleoplasm]p-7Y-KIT [plasmamembrane]SRC-1 [cytosol]KITLG-1(26-190)[extracellularregion]p-7Y-KIT [plasmamembrane]CHEK1 [cytosol]GRB7 [cytosol]PIP3 activates AKTsignalingPI(4,5)P2p-7Y-KIT [plasmamembrane]SOS1 [cytosol]LYN(2-512) [cytosol]PI3K:p-KIT:sSCFdimer:p-KITATPHRAS(1-186) [plasmamembrane]p-Y629-SH2B2[cytosol]LCK [cytosol]p21 RAS:GTPADPp-Y546,Y584-PTPN11[cytosol]RAC1-GTPSRC-1 [cytosol]ATPSTAT3 [cytosol]YES1(2-543)[cytosol]SOCS1:p-KIT complexFYN(2-537) [cytosol]Adapter proteinsGRB2-1 [cytosol]KITLG-1(26-190)[extracellularregion]RAC1-GDPLYN(2-512) [cytosol]LYN(2-512) [cytosol]p-7Y-KIT [plasmamembrane]p-Y142,Y160,Y174-VAV1[plasma membrane]SRC-1 [cytosol]KITLG-1(26-190)[extracellularregion]FYN(2-537) [cytosol]LYN(2-512) [cytosol]YES1(2-543)[cytosol]LCK [cytosol]LCK [cytosol]LCK [cytosol]LCK [cytosol]SFKs:p-8Y-KIT:sSCFdimer:p-8Y-KITKITLG-1(26-190)[extracellularregion]YES1(2-543)[cytosol]FYN(2-537) [cytosol]p-Y-GAB2 [cytosol]STAT5B [cytosol]p-S741,S746-KIT[plasma membrane]GDP [cytosol]Endopeptidases forSCF processingp-7Y-KIT [plasmamembrane]LCK [cytosol]LYN(2-512) [cytosol]YES1(2-543)[cytosol]FYN(2-537) [cytosol]LYN(2-512) [cytosol]p-7Y-KIT [plasmamembrane]p-7Y-KIT [plasmamembrane]FYN(2-537) [cytosol]PTPRU(19-1430)SH2B3 [cytosol]PI3K alphaPIK3CA [cytosol]FER [cytosol]p-Y705-STAT3[cytosol]STAT5A [cytosol]p-7Y-KIT [plasmamembrane]PI(3,4,5)P3 [plasmamembrane]SRC-1 [cytosol]HRAS(1-186) [plasmamembrane]FYN(2-537) [cytosol]YES1(2-543)[cytosol]LCK [cytosol]GRB2-1p-Y546,Y584-PTPN11[cytosol]YES1(2-543)[cytosol]GAB2GRB10 [cytosol]RAC1 [cytosol]GRB2:SOS1:p-KITcomplexp-Y705-STAT3[cytosol]FES [cytosol]KRAS(1-186) [plasmamembrane]SOCS6:p-c-Kit:sSCFdimer:p-c-KitYES1(2-543)[cytosol]Adapterproteins:p-KITcomplexPTPRU(19-1430)[plasma membrane]p-7Y-KIT [plasmamembrane]KITLG-1(26-190)[extracellularregion]p-Y699-STAT5B[cytosol]ATPLYN(2-512) [cytosol]SOS1 [cytosol]PTPN11 [cytosol]p-Y694-STAT5A[cytosol]SHP-1:p-c-KitcomplexFYN(2-537) [cytosol]LCK [cytosol]KIT [plasmamembrane]ADPKITLG-1(26-190)[extracellularregion]GRB2-1 [cytosol]LCK [cytosol]SRC-1 [cytosol]p-JAK2:SFKs:p-KITcomplex:p-STATsSRC-1 [cytosol]KIT:sSCF dimerADPKITLG-1(192-273)LYN(2-512) [cytosol]p-7Y-KIT [plasmamembrane]ADPYES1(2-543)[cytosol]p-7Y-KIT [plasmamembrane]p21 RAS:GDPVAV1YES1(2-543)[cytosol]TEC [cytosol]50, 65


Description

Stem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival and differentiation of hematopoetic progenitors, melanocytes and germ cells.(Linnekin 1999, Rönnstrand 2004, Lennartsson and Rönnstrand 2006). The receptor for SCF is KIT, a tyrosine kinase receptor (RTK) closely related to the receptors for platelet derived growth factor receptor, colony stimulating factor 1 (Linnekin 1999) and Flt3 (Rosnet et al. 1991). Four isoforms of c-Kit have been identified in humans. Alternative splicing results in isoforms of KIT differing in the presence or absence of four residues (GNNK) in the extracellular region. This occurs due to the use of an alternate 5' splice donor site. These GNNK+ and GNNK- variants are co-expressed in most tissues; the GNNK- form predominates and was more strongly tyrosine-phosphorylated and more rapidly internalized (Rönnstrand 2004). There are also splice variants that arise from alternative usage of splice acceptor site resulting in the presence or absence of a serine residue (Crosier et al., 1993). Finally, there is an alternative shorter transcript of KIT expressed in postmeiotic germ cells in the testis which encodes a truncated KIT consisting only of the second part of the kinase domain and thus lackig the extracellular and transmembrane domains as well as the first part of the kinase domain (Rossi et al. 1991). Binding of SCF homodimers to KIT results in KIT homodimerization followed by activation of its intrinsic tyrosine kinase activity. KIT stimulation activates a wide array of signalling pathways including MAPK, PI3K and JAK/STAT (Reber et al. 2006, Rönnstrand 2004). Defects of KIT in humans are associated with different genetic diseases and also in several types of cancers like mast cell leukaemia, germ cell tumours, certain subtypes of malignant melanoma and gastrointestinal tumours.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=1433557

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  28. Yi T, Ihle JN.; ''Association of hematopoietic cell phosphatase with c-Kit after stimulation with c-Kit ligand.''; PubMed Europe PMC Scholia
  29. Ross D, Joyner WL.; ''Resting distribution and stimulated translocation of protein kinase C isoforms alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial cells.''; PubMed Europe PMC Scholia
  30. Blechman JM, Lev S, Brizzi MF, Leitner O, Pegoraro L, Givol D, Yarden Y.; ''Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor.''; PubMed Europe PMC Scholia
  31. Mendiaz EA, Chang DG, Boone TC, Grant JR, Wypych J, Aguero B, Egrie JC, Langley KE.; ''Epitope mapping and immunoneutralization of recombinant human stem-cell factor.''; PubMed Europe PMC Scholia
  32. Craig AW, Greer PA.; ''Fer kinase is required for sustained p38 kinase activation and maximal chemotaxis of activated mast cells.''; PubMed Europe PMC Scholia
  33. Lev S, Yarden Y, Givol D.; ''A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses.''; PubMed Europe PMC Scholia
  34. Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J.; ''Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway.''; PubMed Europe PMC Scholia
  35. Deberry C, Mou S, Linnekin D.; ''Stat1 associates with c-kit and is activated in response to stem cell factor.''; PubMed Europe PMC Scholia
  36. Serve H, Hsu YC, Besmer P.; ''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.''; PubMed Europe PMC Scholia
  37. Crespo P, Schuebel KE, Ostrom AA, Gutkind JS, Bustelo XR.; ''Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product.''; PubMed Europe PMC Scholia
  38. Lennartsson J, Rönnstrand L.; ''The stem cell factor receptor/c-Kit as a drug target in cancer.''; PubMed Europe PMC Scholia
  39. Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
  40. Chian R, Young S, Danilkovitch-Miagkova A, Rönnstrand L, Leonard E, Ferrao P, Ashman L, Linnekin D.; ''Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant.''; PubMed Europe PMC Scholia
  41. Rönnstrand L.; ''Signal transduction via the stem cell factor receptor/c-Kit.''; PubMed Europe PMC Scholia
  42. Roskoski R.; ''Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.''; PubMed Europe PMC Scholia
  43. Taniguchi Y, London R, Schinkmann K, Jiang S, Avraham H.; ''The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and Is associated with the c-Kit receptor.''; PubMed Europe PMC Scholia
  44. Rao N, Dodge I, Band H.; ''The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine kinase signaling in the immune system.''; PubMed Europe PMC Scholia
  45. Lennartsson J, Wernstedt C, Engström U, Hellman U, Rönnstrand L.; ''Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk.''; PubMed Europe PMC Scholia
  46. Plotnikov A, Zehorai E, Procaccia S, Seger R.; ''The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.''; PubMed Europe PMC Scholia
  47. Koyasu S.; ''The role of PI3K in immune cells.''; PubMed Europe PMC Scholia
  48. Yu M, Luo J, Yang W, Wang Y, Mizuki M, Kanakura Y, Besmer P, Neel BG, Gu H.; ''The scaffolding adapter Gab2, via Shp-2, regulates kit-evoked mast cell proliferation by activating the Rac/JNK pathway.''; PubMed Europe PMC Scholia
  49. Jahn T, Seipel P, Urschel S, Peschel C, Duyster J.; ''Role for the adaptor protein Grb10 in the activation of Akt.''; PubMed Europe PMC Scholia
  50. Weiler SR, Mou S, DeBerry CS, Keller JR, Ruscetti FW, Ferris DK, Longo DL, Linnekin D.; ''JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor.''; PubMed Europe PMC Scholia
  51. Brizzi MF, Dentelli P, Lanfrancone L, Rosso A, Pelicci PG, Pegoraro L.; ''Discrete protein interactions with the Grb2/c-Cbl complex in SCF- and TPO-mediated myeloid cell proliferation.''; PubMed Europe PMC Scholia
  52. Cargnello M, Roux PP.; ''Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.''; PubMed Europe PMC Scholia
  53. Alai M, Mui AL, Cutler RL, Bustelo XR, Barbacid M, Krystal G.; ''Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells.''; PubMed Europe PMC Scholia
  54. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
  55. Duronio V, Welham MJ, Abraham S, Dryden P, Schrader JW.; ''p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein.''; PubMed Europe PMC Scholia
  56. Philo JS, Wen J, Wypych J, Schwartz MG, Mendiaz EA, Langley KE.; ''Human stem cell factor dimer forms a complex with two molecules of the extracellular domain of its receptor, Kit.''; PubMed Europe PMC Scholia
  57. Roskoski R.; ''ERK1/2 MAP kinases: structure, function, and regulation.''; PubMed Europe PMC Scholia
  58. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA.; ''Mutations of the BRAF gene in human cancer.''; PubMed Europe PMC Scholia
  59. Price DJ, Rivnay B, Fu Y, Jiang S, Avraham S, Avraham H.; ''Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes.''; PubMed Europe PMC Scholia
  60. Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, McRee DE.; ''Structure of a c-kit product complex reveals the basis for kinase transactivation.''; PubMed Europe PMC Scholia
  61. Zhang Z, Zhang R, Joachimiak A, Schlessinger J, Kong XP.; ''Crystal structure of human stem cell factor: implication for stem cell factor receptor dimerization and activation.''; PubMed Europe PMC Scholia
  62. Kyriakis JM, Avruch J.; ''Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.''; PubMed Europe PMC Scholia
  63. Hafizi S, Dahlbäck B.; ''Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases.''; PubMed Europe PMC Scholia
  64. Longley BJ, Tyrrell L, Ma Y, Williams DA, Halaban R, Langley K, Lu HS, Schechter NM.; ''Chymase cleavage of stem cell factor yields a bioactive, soluble product.''; PubMed Europe PMC Scholia
  65. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
  66. Wellbrock C, Karasarides M, Marais R.; ''The RAF proteins take centre stage.''; PubMed Europe PMC Scholia
  67. Kawaguchi N, Horiuchi K, Becherer JD, Toyama Y, Besmer P, Blobel CP.; ''Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19.''; PubMed Europe PMC Scholia
  68. Timokhina I, Kissel H, Stella G, Besmer P.; ''Kit signaling through PI 3-kinase and Src kinase pathways: an essential role for Rac1 and JNK activation in mast cell proliferation.''; PubMed Europe PMC Scholia
  69. Liu H, Chen X, Focia PJ, He X.; ''Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases.''; PubMed Europe PMC Scholia
  70. Nicholson PR, Empereur S, Glover HR, Dilworth SM.; ''ShcA tyrosine phosphorylation sites can replace ShcA binding in signalling by middle T-antigen.''; PubMed Europe PMC Scholia
  71. Argetsinger LS, Kouadio JL, Steen H, Stensballe A, Jensen ON, Carter-Su C.; ''Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity.''; PubMed Europe PMC Scholia
  72. Kozlowski M, Larose L, Lee F, Le DM, Rottapel R, Siminovitch KA.; ''SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain.''; PubMed Europe PMC Scholia
  73. Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A.; ''APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl.''; PubMed Europe PMC Scholia
  74. Reber L, Da Silva CA, Frossard N.; ''Stem cell factor and its receptor c-Kit as targets for inflammatory diseases.''; PubMed Europe PMC Scholia
  75. Ning ZQ, Li J, McGuinness M, Arceci RJ.; ''STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity.''; PubMed Europe PMC Scholia
  76. Sun J, Pedersen M, Rönnstrand L.; ''Gab2 is involved in differential phosphoinositide 3-kinase signaling by two splice forms of c-Kit.''; PubMed Europe PMC Scholia
  77. Sun J, Pedersen M, Bengtsson S, Rönnstrand L.; ''Grb2 mediates negative regulation of stem cell factor receptor/c-Kit signaling by recruitment of Cbl.''; PubMed Europe PMC Scholia
  78. Argetsinger LS, Stuckey JA, Robertson SA, Koleva RI, Cline JM, Marto JA, Myers MG, Carter-Su C.; ''Tyrosines 868, 966, and 972 in the kinase domain of JAK2 are autophosphorylated and required for maximal JAK2 kinase activity.''; PubMed Europe PMC Scholia
  79. Edling CE, Hallberg B.; ''c-Kit--a hematopoietic cell essential receptor tyrosine kinase.''; PubMed Europe PMC Scholia
  80. Crosier PS, Ricciardi ST, Hall LR, Vitas MR, Clark SC, Crosier KE.; ''Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia.''; PubMed Europe PMC Scholia
  81. Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S.; ''Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand.''; PubMed Europe PMC Scholia
  82. Blume-Jensen P, Rönnstrand L, Gout I, Waterfield MD, Heldin CH.; ''Modulation of Kit/stem cell factor receptor-induced signaling by protein kinase C.''; PubMed Europe PMC Scholia
  83. Liu SK, McGlade CJ.; ''Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc.''; PubMed Europe PMC Scholia
  84. Brizzi MF, Dentelli P, Rosso A, Yarden Y, Pegoraro L.; ''STAT protein recruitment and activation in c-Kit deletion mutants.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
101337view11:22, 1 November 2018ReactomeTeamreactome version 66
100875view20:56, 31 October 2018ReactomeTeamreactome version 65
100416view19:30, 31 October 2018ReactomeTeamreactome version 64
99966view16:14, 31 October 2018ReactomeTeamreactome version 63
99520view14:49, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99162view12:41, 31 October 2018ReactomeTeamreactome version 62
93973view13:49, 16 August 2017ReactomeTeamreactome version 61
93574view11:27, 9 August 2017ReactomeTeamreactome version 61
87186view08:05, 19 July 2016EgonwOntology Term : 'signaling pathway' added !
86676view09:23, 11 July 2016ReactomeTeamreactome version 56
83115view10:00, 18 November 2015ReactomeTeamVersion54
81455view12:59, 21 August 2015ReactomeTeamVersion53
76929view08:20, 17 July 2014ReactomeTeamFixed remaining interactions
76634view12:00, 16 July 2014ReactomeTeamFixed remaining interactions
75964view10:02, 11 June 2014ReactomeTeamRe-fixing comment source
75667view10:57, 10 June 2014ReactomeTeamReactome 48 Update
75022view13:53, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74666view08:43, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
APS

dimer:p-c-Kit:SFKs

complex		ComplexREACT_111288 (Reactome)
APS dimerComplexREACT_111367 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
Adapter

proteins:p-KIT

complex		ComplexREACT_111421 (Reactome)
Adapter proteinsProteinREACT_111747 (Reactome)
CBL [cytosol]ProteinP22681 (Uniprot-TrEMBL)
CBL:Grb2/p-APS:p-c-Kit complexComplexREACT_111310 (Reactome)
CBLProteinP22681 (Uniprot-TrEMBL)
CHEK1 [cytosol]ProteinO14757 (Uniprot-TrEMBL)
Endopeptidases for SCF processingProteinREACT_111360 (Reactome)
FER [cytosol]ProteinP16591 (Uniprot-TrEMBL)
FES [cytosol]ProteinP07332 (Uniprot-TrEMBL)
FYN(2-537) [cytosol]ProteinP06241 (Uniprot-TrEMBL)
GAB2 [cytosol]ProteinQ9UQC2 (Uniprot-TrEMBL)
GAB2:GRB2:p-SHP2:p-KIT complexComplexREACT_111599 (Reactome)
GAB2ProteinQ9UQC2 (Uniprot-TrEMBL)
GDP [cytosol]MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRAP [cytosol]ProteinQ13588 (Uniprot-TrEMBL)
GRAP2 [cytosol]ProteinO75791 (Uniprot-TrEMBL)
GRB10 [cytosol]ProteinQ13322 (Uniprot-TrEMBL)
GRB2-1 [cytosol]ProteinP62993-1 (Uniprot-TrEMBL)
GRB2-1ProteinP62993-1 (Uniprot-TrEMBL)
GRB2:SOS1:p-KIT complexComplexREACT_111435 (Reactome)
GRB2:SOS1ComplexREACT_4435 (Reactome)
GRB2:p-SHP2:p-KIT complexComplexREACT_111665 (Reactome)
GRB7 [cytosol]ProteinQ14451 (Uniprot-TrEMBL)
GTP [cytosol]MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
Grb2:SOS:p-c-Kit/p-APS:p-c-Kit complexComplexREACT_111576 (Reactome)
HRAS(1-186) [plasma membrane]ProteinP01112 (Uniprot-TrEMBL)
JAK2 [cytosol]ProteinO60674 (Uniprot-TrEMBL)
JAK2:SFKS:p-KIT complexComplexREACT_111373 (Reactome)
JAK2ProteinO60674 (Uniprot-TrEMBL)
KIT [plasma membrane]ProteinP10721 (Uniprot-TrEMBL)
KIT:sSCF dimer:KITComplexREACT_111669 (Reactome)
KIT:sSCF dimerComplexREACT_111507 (Reactome)
KITLG-1(192-273)ProteinP21583-1 (Uniprot-TrEMBL)
KITLG-1(26-190)

[extracellular

region]		ProteinP21583-1 (Uniprot-TrEMBL)
KITLG-1(26-190)ProteinP21583-1 (Uniprot-TrEMBL)
KITLG-1ProteinP21583-1 (Uniprot-TrEMBL)
KITProteinP10721 (Uniprot-TrEMBL)
KRAS(1-186) [plasma membrane]ProteinP01116 (Uniprot-TrEMBL)
LCK [cytosol]ProteinP06239 (Uniprot-TrEMBL)
LNK:p-7Y-KIT:sSCF dimer:p-7Y-KITComplexREACT_111280 (Reactome)
LYN(2-512) [cytosol]ProteinP07948 (Uniprot-TrEMBL)
NRAS [plasma membrane]ProteinP01111 (Uniprot-TrEMBL)
P13K:p(Y)-GAB2:GRB2:p-SHP2:p-KIT complexComplexREACT_111874 (Reactome)
PI(3,4,5)P3 [plasma membrane]MetaboliteCHEBI:16618 (ChEBI)
PI(3,4,5)P3MetaboliteCHEBI:16618 (ChEBI)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PI3K alphaComplexREACT_12697 (Reactome)
PI3K:p-KIT:sSCF dimer:p-KITComplexREACT_111423 (Reactome)
PIK3CA [cytosol]ProteinP42336 (Uniprot-TrEMBL)
PIP3 activates AKT signalingPathwayWP2653 (WikiPathways) Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007.
PRKCA [cytosol]ProteinP17252 (Uniprot-TrEMBL)
PRKCAProteinP17252 (Uniprot-TrEMBL)
PTPN11 [cytosol]ProteinQ06124 (Uniprot-TrEMBL)
PTPN11ProteinQ06124 (Uniprot-TrEMBL)
PTPN6 [cytosol]ProteinP29350 (Uniprot-TrEMBL)
PTPN6ProteinP29350 (Uniprot-TrEMBL)
PTPRO:KITComplexREACT_111289 (Reactome)
PTPRU(19-1430) [plasma membrane]ProteinQ92729 (Uniprot-TrEMBL)
PTPRU(19-1430)ProteinQ92729 (Uniprot-TrEMBL)
RAC1 [cytosol]ProteinP63000 (Uniprot-TrEMBL)
RAC1-GDPComplexREACT_22018 (Reactome)
RAC1-GTPComplexREACT_21594 (Reactome)
RAF/MAP kinase cascadePathwayWP2735 (WikiPathways) The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
SFKs:p-8Y-KIT:sSCF dimer:p-8Y-KITComplexREACT_111437 (Reactome)
SFKs:p-KIT complexComplexREACT_111322 (Reactome)
SH2B2 [cytosol]ProteinO14492 (Uniprot-TrEMBL)
SH2B3 [cytosol]ProteinQ9UQQ2 (Uniprot-TrEMBL)
SH2B3ProteinQ9UQQ2 (Uniprot-TrEMBL)
SHP-1:p-c-Kit complexComplexREACT_111525 (Reactome)
SHP2:SFKs:p-KIT:sSCF dimer:p-KITComplexREACT_111414 (Reactome)
SOCS1 [cytosol]ProteinO15524 (Uniprot-TrEMBL)
SOCS1:p-KIT complexComplexREACT_111392 (Reactome)
SOCS1ProteinO15524 (Uniprot-TrEMBL)
SOCS6 [cytosol]ProteinO14544 (Uniprot-TrEMBL)
SOCS6:p-c-Kit:sSCF dimer:p-c-KitComplexREACT_111256 (Reactome)
SOCS6ProteinO14544 (Uniprot-TrEMBL)
SOS1 [cytosol]ProteinQ07889 (Uniprot-TrEMBL)
SRC-1 [cytosol]ProteinP12931-1 (Uniprot-TrEMBL)
STAT1 [cytosol]ProteinP42224 (Uniprot-TrEMBL)
STAT3 [cytosol]ProteinP40763 (Uniprot-TrEMBL)
STAT5A [cytosol]ProteinP42229 (Uniprot-TrEMBL)
STAT5B [cytosol]ProteinP51692 (Uniprot-TrEMBL)
STATsProteinREACT_111833 (Reactome)
Src family tyrosine kinases (SFKs)ProteinREACT_13328 (Reactome)
TEC [cytosol]ProteinP42680 (Uniprot-TrEMBL)
Tyrosine

kinases:p-KIT

complex		ComplexREACT_111354 (Reactome)
Tyrosine kinasesProteinREACT_111786 (Reactome)
VAV1ProteinP15498 (Uniprot-TrEMBL)
YES1(2-543) [cytosol]ProteinP07947 (Uniprot-TrEMBL)
p(Y)-GAB2:GRB2:p-SHP2:p-KIT complexComplexREACT_111870 (Reactome)
p-7Y-KIT [plasma membrane]ProteinP10721 (Uniprot-TrEMBL)
p-7Y-KIT:sSCF dimer:p-7Y-KITComplexREACT_111273 (Reactome)
p-8Y-KIT [plasma membrane]ProteinP10721 (Uniprot-TrEMBL)
p-APS dimer:p-KIT complexComplexREACT_111587 (Reactome)
p-JAK2:SFKs:p-KIT complex:STATsComplexREACT_111888 (Reactome)
p-JAK2:SFKs:p-KIT

complex:p-STAT

dimers		ComplexREACT_111313 (Reactome)
p-JAK2:SFKs:p-KIT complex:p-STATsComplexREACT_111763 (Reactome)
p-JAK2:SFKs:p-KIT complexComplexREACT_111294 (Reactome)
p-KIT (S741,746):PKC alphaComplexREACT_111348 (Reactome)
p-S741,S746-KIT [plasma membrane]ProteinP10721 (Uniprot-TrEMBL)
p-SHP2:p-KIT complexComplexREACT_111317 (Reactome)
p-STAT dimersComplexREACT_111683 (Reactome)
p-VAV1:PIP3ComplexREACT_111383 (Reactome)
p-Y-GAB2 [cytosol]ProteinQ9UQC2 (Uniprot-TrEMBL)
p-Y1007-JAK2 [cytosol]ProteinO60674 (Uniprot-TrEMBL)
p-Y142,Y160,Y174-VAV1 [plasma membrane]ProteinP15498 (Uniprot-TrEMBL)
p-Y546,Y584-PTPN11 [cytosol]ProteinQ06124 (Uniprot-TrEMBL)
p-Y629-SH2B2 [cytosol]ProteinO14492 (Uniprot-TrEMBL)
p-Y694-STAT5A [cytosol]ProteinP42229 (Uniprot-TrEMBL)
p-Y694-STAT5A [nucleoplasm]ProteinP42229 (Uniprot-TrEMBL)
p-Y699-STAT5B [cytosol]ProteinP51692 (Uniprot-TrEMBL)
p-Y699-STAT5B [nucleoplasm]ProteinP51692 (Uniprot-TrEMBL)
p-Y701-STAT1-1 [cytosol]ProteinP42224-1 (Uniprot-TrEMBL)
p-Y701-STAT1-1 [nucleoplasm]ProteinP42224-1 (Uniprot-TrEMBL)
p-Y705-STAT3 [cytosol]ProteinP40763 (Uniprot-TrEMBL)
p-Y705-STAT3 [nucleoplasm]ProteinP40763 (Uniprot-TrEMBL)
p21 RAS:GDPComplexREACT_2657 (Reactome)
p21 RAS:GTPComplexREACT_4782 (Reactome)
sSCF dimerComplexREACT_111693 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_111042 (Reactome)
ADPArrowREACT_111070 (Reactome)
ADPArrowREACT_111072 (Reactome)
ADPArrowREACT_111081 (Reactome)
ADPArrowREACT_111103 (Reactome)
ADPArrowREACT_111112 (Reactome)
ADPArrowREACT_111152 (Reactome)
ADPArrowREACT_111186 (Reactome)
ADPArrowREACT_111196 (Reactome)
ADPArrowREACT_111244 (Reactome)
APS

dimer:p-c-Kit:SFKs

complex		ArrowREACT_111199 (Reactome)
APS

dimer:p-c-Kit:SFKs

complex		REACT_111112 (Reactome)
APS

dimer:p-c-Kit:SFKs

complex		mim-catalysisREACT_111112 (Reactome)
APS dimerREACT_111199 (Reactome)
ATPREACT_111042 (Reactome)
ATPREACT_111070 (Reactome)
ATPREACT_111072 (Reactome)
ATPREACT_111081 (Reactome)
ATPREACT_111103 (Reactome)
ATPREACT_111112 (Reactome)
ATPREACT_111152 (Reactome)
ATPREACT_111186 (Reactome)
ATPREACT_111196 (Reactome)
ATPREACT_111244 (Reactome)
Adapter

proteins:p-KIT

complex		ArrowREACT_111192 (Reactome)
Adapter proteinsREACT_111192 (Reactome)
CBL:Grb2/p-APS:p-c-Kit complexArrowREACT_111179 (Reactome)
CBLREACT_111179 (Reactome)
Endopeptidases for SCF processingmim-catalysisREACT_111098 (Reactome)
GAB2:GRB2:p-SHP2:p-KIT complexArrowREACT_111237 (Reactome)
GAB2:GRB2:p-SHP2:p-KIT complexREACT_111186 (Reactome)
GAB2:GRB2:p-SHP2:p-KIT complexmim-catalysisREACT_111186 (Reactome)
GAB2REACT_111237 (Reactome)
GDPArrowREACT_111091 (Reactome)
GDPArrowREACT_111195 (Reactome)
GRB2-1REACT_111069 (Reactome)
GRB2:SOS1:p-KIT complexArrowREACT_111200 (Reactome)
GRB2:SOS1:p-KIT complexmim-catalysisREACT_111091 (Reactome)
GRB2:SOS1REACT_111200 (Reactome)
GRB2:p-SHP2:p-KIT complexArrowREACT_111069 (Reactome)
GRB2:p-SHP2:p-KIT complexREACT_111237 (Reactome)
GTPREACT_111091 (Reactome)
GTPREACT_111195 (Reactome)
Grb2:SOS:p-c-Kit/p-APS:p-c-Kit complexREACT_111179 (Reactome)
JAK2:SFKS:p-KIT complexArrowREACT_111205 (Reactome)
JAK2:SFKS:p-KIT complexREACT_111070 (Reactome)
JAK2:SFKS:p-KIT complexmim-catalysisREACT_111070 (Reactome)
JAK2REACT_111205 (Reactome)
KIT:sSCF dimer:KITArrowREACT_111210 (Reactome)
KIT:sSCF dimer:KITREACT_111103 (Reactome)
KIT:sSCF dimer:KITmim-catalysisREACT_111103 (Reactome)
KIT:sSCF dimerArrowREACT_111051 (Reactome)
KIT:sSCF dimerREACT_111210 (Reactome)
KITLG-1(192-273)ArrowREACT_111098 (Reactome)
KITLG-1(26-190)ArrowREACT_111098 (Reactome)
KITLG-1(26-190)REACT_111044 (Reactome)
KITLG-1REACT_111098 (Reactome)
KITREACT_111051 (Reactome)
KITREACT_111127 (Reactome)
KITREACT_111196 (Reactome)
KITREACT_111210 (Reactome)
LNK:p-7Y-KIT:sSCF dimer:p-7Y-KITArrowREACT_111099 (Reactome)
P13K:p(Y)-GAB2:GRB2:p-SHP2:p-KIT complexArrowREACT_111036 (Reactome)
PI(3,4,5)P3ArrowREACT_111081 (Reactome)
PI(3,4,5)P3REACT_111072 (Reactome)
PI(4,5)P2REACT_111081 (Reactome)
PI3K alphaREACT_111036 (Reactome)
PI3K alphaREACT_111146 (Reactome)
PI3K:p-KIT:sSCF dimer:p-KITArrowREACT_111146 (Reactome)
PI3K:p-KIT:sSCF dimer:p-KITmim-catalysisREACT_111081 (Reactome)
PRKCAREACT_111196 (Reactome)
PRKCAmim-catalysisREACT_111196 (Reactome)
PTPN11REACT_111049 (Reactome)
PTPN6REACT_111223 (Reactome)
PTPRO:KITArrowREACT_111127 (Reactome)
PTPRU(19-1430)REACT_111127 (Reactome)
RAC1-GDPREACT_111195 (Reactome)
RAC1-GTPArrowREACT_111195 (Reactome)
REACT_111036 (Reactome) Phosphorylated GAB2 recruits the p85 subunit of the PI3K complex and activates the PI3K/AKT pathway. This is one of two mechanisms described for the recruitment of PI3K to KIT.
REACT_111042 (Reactome) Src family of tyrosine kinases phosphorylate KIT on Y900 located in the second part of the tyrosine kinase domain. This phosphorylated tyrosine acts as a docking site for p85alpha regulatory subunit of PI3K and the adapter protein CRKII. CRKII does not interact directly with KIT but is recruited indirectly by binding to p85alpha subunit of PI3K. Thus, in this case the p85 subunit acts as an adapter between KIT and CRKII, and not to recruit PI3-kinase. (Lennartsson et al. 2003).
REACT_111044 (Reactome) sSCF exists as noncovalently associated homodimer composed of two monomers interacting head-to-head to form an elongated, slightly bent dimer. Dimerization of sSCF is a dynamic process and it may play a regulatory role in the dimerization and activation of KIT (Zhang et al, 2000; Philo et al, 1996).
REACT_111049 (Reactome) SHP2 is a protein tyrosine phosphatase (PTP) with two NH2-terminal SH2 domains, a PTP domain, a -COOH tail with two tyrosyl phosphorylation sites at Y546 and Y584, and an interposed proline-rich domain. SHP2 binds to activated KIT on tyrosine-568 in the juxtamembrane region, which also constitutes the docking site for a number of other signal transduction molecules, such as SFKs, Csk homologous kinase (CHK), CBL, LNK and Adapter protein with PH and SH2 domains (APS) (Kozlowski et al. 1998, Price et al. 1997, Gueller et al. 2008).
REACT_111051 (Reactome) Two human isoforms of KIT have been identified, resulting from alternative splicing. They are characterized by the presence or absence of a tetrapeptide sequence (GNNK 510-513 aa) in the extracellular part of the juxtamembrane region and designated GNNK+ (Kit) or GNNK- (KitA) (Piao et al. 1994). The isoforms are co-expressed in most tisuues, with the GNNK- form predominating (Reith et al. 1991). No difference in ligand affinity was observed (Caruana et al. 1999).
KIT belongs to the type III tyrosine kinase receptor family, with five extracellular immunoglobulin (Ig)-like domains, a single transmembrane region, an inhibitory cytoplasmic juxtamembrane domain, and a split cytoplasmic kinase domain separated by a kinase insert segment and a cytoplasmic tail (Mol et al. 2003).
Signaling by KIT occurs following SCF binding. SCF homodimers binds to the first three Ig-like domains of KIT in the regions between aa L104-D122 and R146-D153 (Mendiaz et al. 1996, Matous et al. 1996) which leads to dimerization which is further stabilized by Ig-like domains 3-4 (Yuzawa et al., 2007).
REACT_111069 (Reactome) GRB2 can be recruited indirectly to KIT through SHP2 (Tauchi et al. 1994). Y279, Y304, Y546 and Y584 (usually referred to as Y542 and Y580 in literature based on the SHP2 short isoform) are the potential sites of SHP2 tyrosyl phosphorylation and that Y546 is the major GRB2 binding site (Feng, et al. 1993, Araki, et al. 2003). This brings Grb2:SOS1 into proximity with the plasma membrane, where it can activate Ras.
REACT_111070 (Reactome) SCF induces rapid and transient autophosphorylation of JAK2 bound to c-KIT. JAKs bound to activated, dimerized receptors cross-phosphorylate and thereby activate each other. Multiple phosphorylation sites have been identified in JAK2 (tyrosines 221, 570, 868, 966, 972, 1007 and 1008 ) of which phosphorylation of tyrosine 1007 is essential for kinase activity (Feng et al 1997, Argetsinger et al. 2004, 2010). Tyrosine 1007 is in the activation loop and phosphorylation allows access of the catalytic loop to the ATP in the ATP binding domain. Of all the predicted phoshorylation sites only the critical tyrosine 1007 is represented in the reaction.
REACT_111072 (Reactome) The Src and PI3-kinase signaling pathways converge to activate Rac1 and JNK after c-Kit activation, promoting mast cell proliferation but not for suppression of apoptosis (Timokhina et al. 1998). PI3K and Src are considered mediators of c-Kit induced Rac1 activation via the guanine nucleotide exchange factor (GEF) VAV1. Stimulation of c-Kit receptor results in rapid tyrosine phosphorylation of VAV1 (Timokhina et al. 1998).
VAV1 exists in an auto-inhibitory state folded in such a way as to inhibit the GEF activity of its Dbl homology domain (DH) domain. PI3K is thought to modulate the activation of VAV1 by influencing its degree of tyrosine phosphorylation and its recruitment to membrane. VAV1 is recruited to membrane by binding to PtdIns(3,4,5)P3 (PIP3) and this interaction relieves an intramolecular interaction between pleckstrin homology (PH) and DH domains, thus facilitating tyrosine phosphorylation on Y174 and so further opening of the DH/PH domains, binding of Rac-GDP and catalysis (Welch et al, 2003). In VAV1, tyrosine 174 (Y174) binds to the DH domain and inhibits its GEF activity. Src kinases phosphorylate this Y174 and this causes the tyrosine to move away from the DH domain thereby reliving the auto-inhibition.
REACT_111081 (Reactome) PI3 kinases catalyze the production of phosphatidylinositol-3, 4, 5-triphosphate (PIP3) by phosphorylating phosphatidylinositol-4, 5-bisphosphate (PIP2). PIP3 bound to the inner lipid bilayer of the plasma membrane promotes the recruitment and activation of AKT. Active AKT subsequently phosphorylates the pro-apoptotic factor Bad at Ser136 which leads to it binding 14-3-3 protein and sequestering from the anti-apoptotic molecules Bcl-XL therby reducing antiapoptotic events and promoting cell survival. The alternative route for c-Kit mediated survival is through AKT-mediated phosphorylation and incativation of the forkhead transcription factor (FoxO3a) (Engstrom et al, 2003; Lennartson et al , 2005).
REACT_111091 (Reactome) Once recruited to the membrane in response to c-Kit stimulation, Son of sevenless (SOS1) activates the small GTPase protein Ras. SOS1 is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases. SOS1 activates Ras by binding which induces a conformational change that causes the exchange of GDP with GTP. Ras proteins are membrane-bound GTPases that regulate crucial cellular processes such as growth, proliferation and differentiation. Active Ras-GTP stimulates multiple effector proteins such as Raf-1, which induce a variety of cellular responses, including initiation of mitogen activated protein kinase (MAPK) cascade signaling.
REACT_111098 (Reactome) SCF exists as two alternatively spliced variants, a soluble form and a membrane-bound form differing in one exon (exon 6). Both isoforms are initially membrane bound with an extracellular domain, a transmembrane segment and an intracellular region. The longer isoform is rapidly cleaved to generate a 165 aa soluble protein knows as sSCF. The SCF transcript that lacks exon 6 encodes a glycoprotein that remains membrane-bound (mSCF). Both mSCF and sSCF are bioactive but different in their efficacy in c-kit activation.
Proteases including matrix metalloprotease-9 (Heissig et al., 2002), Chymase-1 (Longley et al., 1997) and several members of the ADAMs family (Kawaguchi et al, 2007; Amour et al, 2002; Chesneau et al, 2003; Mohan et al, 2002; Roghani et al, 1999; Zou et al, 2004) have been suggested to have a role in the processing of sSCF.
REACT_111099 (Reactome) The adaptor protein LNK with its SH2 domain binds to the juxtamembrane domain (amino acids 544-577) of KIT on Y568 and inhibit the downstream signalling (Gueller et al. 2008).
REACT_111100 (Reactome) SOCS1 has been identified as a KIT binding partner from the yeast two-hybrid system (Sepulveda et al, 1999). SOCS1 expression is induced upon KIT activation. It associates with KIT via its SH2 domain. SOCS1 does not inhibit KIT kinase activity directly, instead it binds to GRB2 and VAV1, and selectively inhibits SCF-induced proliferation, while not effecting survival signal (Sepulveda et al, 1999). It has been proposed that SOCS1 may interrupt signal transduction pathways downstream of JAK2 (Sepulveda et al, 1999).
REACT_111103 (Reactome) 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.
REACT_111112 (Reactome) APS bound to KIT is phosphorylated by tyrosine kinases in response to SCF stimulation (Wollberg et al, 2003). The C-terminal tyrosine 629 may be the target site of phosphorylation in APS (Wakioka et al, 1999).
REACT_111127 (Reactome) Tyrosine phosphatase PTPRO associates constitutively with c-Kit independently of SCF stimulation. PTPRO undergoes phosphorylation upon SCF stimulation. The PTPRO binding site on c-Kit and the molecular mechanism by which c-Kit signaling is regulated by PTPRO have not been determined.
REACT_111136 (Reactome) Activation of KIT mediates the recruitment of and association with STAT1alpha, STAT3, STAT5A and STAT5B (Deberry et al. 1997, Brizzi et al. 1999, Rönnstrand 2004).
REACT_111146 (Reactome) The regulatory subunit (p85) of PI3K interacts directly with phosphorylated Y721 of KIT via one of its SH2 domains. This binding leads to the activation of the catalytic domain (p110) of PI3K. SCF-induced PI3K recruitment mediates AKT activation through phospholipids at the membrane and to subsequent phosphorylation of the pro-apoptotic factor Bad as well as Fox3a.
PI3K activation mediates SCF-induced cell proliferation, survival, differentiation, adhesion, secretion and actin cytoskeletal organization.
REACT_111152 (Reactome) Following association with KIT, Tauchi et al. had observed phosphorylation of SHP2 (Tauchi et al. 1994). Tyrosine residues Y546 and Y584 (usually referred to as Y542 and Y580 in literature based on the short isoform) are the major sites of SHP2 tyrosyl phosphorylation. Src family kinases (SFKs) are candidates for this phosphorylation (Araki et al. 2003). The phosphorylated tyrosine residues on SHP2 can recruit the adapter protein GRB2 (Tauchi et al. 1994), but it is unclear whether GRB2 binding to SHP2 is important for KIT mediated SHP2 signaling or whether the effect of SHP2 on the RAS/ERK pathway goes through its catalytic activity.
REACT_111179 (Reactome) The phosphotyrosine residue in APS creates a putative binding site for CBL. CBL is an ubiquitin E3 ligase that attaches ubiquitin to KIT leading to KIT's ubiquitination followed by internalization and degradation. GRB2 in addition to its role in positive signaling via RAS/ERK pathway also mediates negative regulation of KIT by recruiting CBL (Sun et al, 2007). CBL has also been shown to bind directly to both Y568 and Y936 in KIT (Masson et al. 2006). CBL bound to KIT ubiquitinates KIT and targets it to lysosomal degradation (Masson et al. 2006)
REACT_111182 (Reactome) Phosphorylation on a tyrosine residues immediately distal to the SH2 domain induces STATs homo- or heterodimerization through phosphotyrosine-SH2 interactions.
REACT_111186 (Reactome) GAB2 bound to GRB2 on KIT is then phosphorylated on a number of tyrosine residues through the action of Src family kinases (SFKs).
REACT_111192 (Reactome) Adapter proteins GADS, GRAP, GRB7 and GRB10 interact with activated KIT (Liu & McGlade 1998, Feng et al. 1996, Thömmes et al. 1999, Jahn et al. 2002).
REACT_111195 (Reactome) Vav1, once activated by PIP3 binding and phosphorylation by Src kinases, stimulates the GDP/GTP exchange activity of Rac. Vav1 is selective for Rac and catalyses exchange of bound GDP for GTP.
REACT_111196 (Reactome) Protein kinase C (PKC) alpha phosphorylates and regulates the activity of several receptor tyrosine kinases including KIT. PKC alpha is involved in a negative feedback loop regulating SCF induced proliferation by phosphorylating and inhibiting the kinase activity of KIT (Blume-Jensen et al. 1994, 1995). PKC alpha phosphorylates KIT on S741 and S746 of the kinase insert (Blume-Jensen et al. 1995). This serine phosphorylation inhibits KIT kinase activity and reduces the capacity of multiple SH2 containing signaling components to associate with KIT (Linnekin 1999).
REACT_111199 (Reactome) APS adapter protein has been identified as a KIT binding partner using yeast two-hybrid screening. APS contains a PH domain and an SH2 domain. The SH2 domain interacts with c-Kit phosphotyrosine residues Y568 and Y936 (Wollberg et al. 2003).
REACT_111200 (Reactome) GRB2 is an adapter protein with one SH2 domain and two SH3 domains. It exists in part as a preformed complex with the RAS GDP/GTP exchanger SOS. GRB2 with its SH2 domain binds directly to activated KIT on autophosphorylated sites Y703 and Y936 (Thommes et al. 1999). GRB2 can also be recruited indirectly to KIT by binding KIT downstream signal transduction molecules such as SHP 2, SHC1, GAB1 and GAB2 (Rönnstrand 2004, Linnekin 1999). GRB2:SOS complex bound to KIT then activates the small GTPase protein RAS. It should be noted that not all GRB2 interactions with KIT involves an activation of RAS, but it can also act as an adapter protein for recruiting both GAB2 (Sun et al. 2008) and CBL (Sun et al. 2007) to KIT.
REACT_111205 (Reactome) Janus kinase 2 (JAK2) plays an important role in SCF induced proliferation (Radosevic et al. 2004). JAK2 was observed to pre-associate with KIT, with increased association after SCF stimulation of KIT (Weiler et al. 1996).
REACT_111210 (Reactome) Binding of the SCF dimer to KIT rapidly triggers KIT dimerization and autophosphorylation. It is thought that one SCF dimer binds simultaneously to two KIT monomers. The fourth Ig-like domain of KIT contains the dimerisation site; deletion of this domain completely abolishes KIT dimerisation and subsequent downstream signaling (Edling et al. 2007, Blechman et al. 1995). KIT dimerization is a crucial initial step in the SCF signal transduction process.
REACT_111221 (Reactome) Cytoplasmic tyrosine kinases such as CHK1 (Csk homologous kinase or MATK), FER and FES associate with p-KIT upon SCF stimulation (Price et al, 19997; Jhun et al, 1995; Craig AW, Greer PA, 2002). TEC has been demonstrated to associate with KIT constitutively and is activated by ligand stimulation (Tang et a l. 1994).
REACT_111223 (Reactome) The protein tyrosine phosphatase SHP-1 negatively regulates KIT signaling through binding to phosphorylated Y570. It is unclear whether SHP1 directly dephosphorylates KIT or elicits dephosphorylation of the receptor indirectly by dephosphorylating and inhibiting cytosolic PTKs that act on KIT. SHP-1 may also compete with and displace SFKs or other proteins that dock to phosphorylated Y570 (Kozlowski et al, 1998).
REACT_111230 (Reactome) SOCS6 protein interacts with the phosphorylated Y568 in the juxtamembrane domain of c-Kit following SCF-stimulated tyrosine phosphorylation. Binding of SOCS6 to Y568 may mask this docking site for Src family kinases and this may inhibit the phosphorylation of p38 and ERK. This negatively regulates c-Kit receptor proliferation signal but not SCF-induced chemotaxis (Bayle et al. 2004, Zadjali et al 2011). Binding of SOCS6 mediates recruitment of elongin B and C to form a ubiquitin E3 ligase complex that leads to ubiquitination of KIT and its degradation (Zadjali et al 2011).
REACT_111237 (Reactome) The scaffolding adapter GAB2 plays a role in KIT dependent PI3K/AKT activation. GAB2 interacts with KIT indirectly via the adapter protein GRB2 which is bound to KIT on phosphorylated Y703 and Y936 (Sun et al. 2008, Yu et al. 2006).
REACT_111242 (Reactome) After dimerization STAT dimers release from the receptor complex and migrate to the nucleus for DNA binding. STAT5s/STAT1alpha heterodimeric complexes specifically recognize beta-casein promoter region (PIE) (Brizzi et al. 1999). c-Kit dependent JAK/STAT activation is associated with the growth and differentiation of fetal liver haematopoietic progenitor cells (Rönnstrand 2004, Reber et al. 2006).
REACT_111244 (Reactome) JAK2 activation results in the phosphorylation and activation of STAT1alpha, STAT3, STAT5A and STAT5B (Deberry et al. 1997, Brizzi et al. 1999, Ning et al. 2001, Ronnstrand 2004). STAT family members can be activated by JAK kinases, receptor tyrosine kinases or SFKs. LYN kinase has been identified to have role in SCF-induced phosphorylation of STAT3 (Shivakrupa & Linnekin 2005).
REACT_111251 (Reactome) Binding of SCF to KIT induces the activation and rapid increase in kinase activity of multiple Src family kinases (SFK), including Src, Lck, Tec, Fyn, and Lyn (Timokhina et al. 1998, Krystal et al. 1998, Linnekin et al. 1997, Lennartsson et al. 1999, Tang et al. 1994, Samayawardhena et al. 2007). The tyrosine residues Y568 and Y570 in KIT juxtamembrane region are involved in the association of SFKs (Price et al. 1997).
SFKs recruited to KIT induce proliferation and chemotaxis in primary hematopoietic progenitor cells or bone marrow derived mast cells (O'Laughlin-Bunner et al. 2001). SCF activated SFKs also mediate a critical signal for lymphocyte development (Agosti et al. 2004). Timokhina et al. demonstrated that Src kinase and PI3-kinase signalling pathways converge to activate Rac1 and JNK after SCF stimulation in BMMC, promoting cell proliferation (Timokhina et al., 1998, Reber et al. 2006 ).
SFKs:p-8Y-KIT:sSCF dimer:p-8Y-KITArrowREACT_111042 (Reactome)
SFKs:p-KIT complexArrowREACT_111251 (Reactome)
SFKs:p-KIT complexREACT_111042 (Reactome)
SFKs:p-KIT complexREACT_111049 (Reactome)
SFKs:p-KIT complexREACT_111199 (Reactome)
SFKs:p-KIT complexREACT_111205 (Reactome)
SFKs:p-KIT complexmim-catalysisREACT_111072 (Reactome)
SH2B3REACT_111099 (Reactome)
SHP-1:p-c-Kit complexArrowREACT_111223 (Reactome)
SHP2:SFKs:p-KIT:sSCF dimer:p-KITArrowREACT_111049 (Reactome)
SHP2:SFKs:p-KIT:sSCF dimer:p-KITREACT_111152 (Reactome)
SHP2:SFKs:p-KIT:sSCF dimer:p-KITmim-catalysisREACT_111152 (Reactome)
SOCS1:p-KIT complexArrowREACT_111100 (Reactome)
SOCS1REACT_111100 (Reactome)
SOCS6:p-c-Kit:sSCF dimer:p-c-KitArrowREACT_111230 (Reactome)
SOCS6REACT_111230 (Reactome)
STATsREACT_111136 (Reactome)
Src family tyrosine kinases (SFKs)REACT_111251 (Reactome)
Tyrosine

kinases:p-KIT

complex		ArrowREACT_111221 (Reactome)
Tyrosine kinasesREACT_111221 (Reactome)
VAV1REACT_111072 (Reactome)
p(Y)-GAB2:GRB2:p-SHP2:p-KIT complexArrowREACT_111186 (Reactome)
p(Y)-GAB2:GRB2:p-SHP2:p-KIT complexREACT_111036 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITArrowREACT_111103 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111099 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111100 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111146 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111192 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111200 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111221 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111223 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111230 (Reactome)
p-7Y-KIT:sSCF dimer:p-7Y-KITREACT_111251 (Reactome)
p-APS dimer:p-KIT complexArrowREACT_111112 (Reactome)
p-JAK2:SFKs:p-KIT complex:STATsArrowREACT_111136 (Reactome)
p-JAK2:SFKs:p-KIT complex:STATsREACT_111244 (Reactome)
p-JAK2:SFKs:p-KIT complex:STATsmim-catalysisREACT_111244 (Reactome)
p-JAK2:SFKs:p-KIT

complex:p-STAT

dimers		ArrowREACT_111182 (Reactome)
p-JAK2:SFKs:p-KIT

complex:p-STAT

dimers		REACT_111242 (Reactome)
p-JAK2:SFKs:p-KIT complex:p-STATsArrowREACT_111244 (Reactome)
p-JAK2:SFKs:p-KIT complex:p-STATsREACT_111182 (Reactome)
p-JAK2:SFKs:p-KIT complexArrowREACT_111070 (Reactome)
p-JAK2:SFKs:p-KIT complexArrowREACT_111242 (Reactome)
p-JAK2:SFKs:p-KIT complexREACT_111136 (Reactome)
p-KIT (S741,746):PKC alphaArrowREACT_111196 (Reactome)
p-KIT (S741,746):PKC alphaTBarREACT_111103 (Reactome)
p-SHP2:p-KIT complexArrowREACT_111152 (Reactome)
p-SHP2:p-KIT complexREACT_111069 (Reactome)
p-STAT dimersArrowREACT_111242 (Reactome)
p-VAV1:PIP3ArrowREACT_111072 (Reactome)
p-VAV1:PIP3mim-catalysisREACT_111195 (Reactome)
p21 RAS:GDPREACT_111091 (Reactome)
p21 RAS:GTPArrowREACT_111091 (Reactome)
sSCF dimerArrowREACT_111044 (Reactome)
sSCF dimerREACT_111051 (Reactome)
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