Signaling by SCF-KIT (Homo sapiens)

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11, 15, 19, 35, 40...29, 5913, 22, 3162, 691, 3, 6, 14, 23...30, 5820, 6511, 36, 434522, 33, 51, 53, 6025, 38389, 12, 22, 27, 47...6346, 598614, 7, 28, 6310, 45, 5622, 42, 43, 483022, 51, 6722, 50-52, 6618451, 142616, 18, 5510, 45385, 30, 44, 5711, 24, 37, 68181, 2, 17, 23p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer Src family tyrosine kinases sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT PTPROKIT sSCF dimer sSCF dimer Src family tyrosine kinases Src family tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer p-APS dimerp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex p-APS dimerp-KIT complex P13KpSrc family tyrosine kinases PI3K alpha p-7Y-KITsSCF dimerp-7Y-KIT CBLGrb2/p-APSp-c-Kit complex GRB2p-SHP2p-KIT complex p-SHP2p-KIT complex Adapter proteinsp-KIT complex GRB2SOS1p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT pp-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT p-STAT dimers p-SHP2p-KIT complex Src family tyrosine kinases p-SHP2p-KIT complex p-STAT dimer Tyrosine kinases sSCF dimer GRB2p-SHP2p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT PI3Kp-KITsSCF dimerp-KIT LNKp-7Y-KITsSCF dimerp-7Y-KIT Tyrosine kinasesp-KIT complex p-8Y-KITsSCF dimerp-8Y-KIT Src family tyrosine kinases sSCF dimer cytosolSFKsp-KIT complex SFKsp-KIT complex p-STATs PI3K alpha nucleoplasmp-SHP2p-KIT complex p-APS dimer Src family tyrosine kinases SFKsp-KIT complex sSCF dimer p-JAK2SFKsp-KIT complexp-STATs sSCF dimer PI3K alpha p-JAK2SFKsp-KIT complex sSCF dimer SFKsp-KIT complex sSCF dimer JAK2SFKSp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer SFKsp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT p-KIT p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer GAB2GRB2p-SHP2p-KIT complex sSCF dimer sSCF dimer sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex SFKsp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT SOCS1p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT SHP2SFKsp-KITsSCF dimerp-KIT RAC1-GDP SFKsp-KIT complex SFKsp-KIT complex SFKsp-KIT complex SFKsp-KIT complex Grb2SOSp-c-Kit/p-APSp-c-Kit complex p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer p-APS dimer sSCF dimer p-STATs SFKsp-8Y-KITsSCF dimerp-8Y-KIT sSCF dimer Src family tyrosine kinases KITsSCF dimerKIT KITsSCF dimer p-JAK2SFKsp-KIT complexSTATs GRB2SOS1p-KIT complex sSCF dimer sSCF dimer SFKsp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases Src family tyrosine kinases Src family tyrosine kinases APS dimer p-7Y-KITsSCF dimerp-7Y-KIT RAC1-GTP APS dimer p21 RAS p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer GRB2SOS1 p-STATs SFKsp-KIT complex SOCS6p-c-KitsSCF dimerp-c-Kit STATs p21 RAS GRB2p-SHP2p-KIT complex Src family tyrosine kinases Src family tyrosine kinases sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT GRB2p-SHP2p-KIT complex p21 RASGTP GRB2SOS1 sSCF dimer sSCF dimer p-JAK2SFKsp-KIT complexp-STAT dimers Src family tyrosine kinases Adapter proteins sSCF dimer p-SHP2p-KIT complex sSCF dimer p21 RASGDP p-7Y-KITsSCF dimerp-7Y-KIT GRB2SOS1 p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases APS dimerp-c-KitSFKs complex SHP-1p-c-Kit complex p-VAV1PIP3 sSCF dimer Src family tyrosine kinases KITLG-1p-Y546,Y584-PTPN11 LYNLCK p-Y701-STAT1-1 p-VAV1PIP3pSOCS1 p-Y629-SH2B2 FYNSOS1 FYNKITSRC-1 p-Y1007-JAK2 STAT5A STAT1 p-JAK2SFKsp-KIT complexp-STATsGRB2-1 LCK PIYES1FYNGDPFES ATPKITLG-1ADPp-Y694-STAT5A SRC-1 FYNLYNADPADPKITLG-1CBLp-7Y-KIT FYNp-Y699-STAT5B p-7Y-KIT KITLG-1LYNp-7Y-KIT KITLG-1p-Y1007-JAK2 YES1LYNTyrosine kinasesYES1PTPN11 YES1SH2B2 LCK LYNp-JAK2SFKsp-KIT complexp-STAT dimersATPFYNGRB2-1 p-7Y-KIT NRAS KITLG-1LYNp-Y699-STAT5B GAB2GRB2p-SHP2p-KIT complexp-Y629-SH2B2 JAK2SFKSp-KIT complexp-Y694-STAT5A APS dimerp-c-KitSFKs complexp-7Y-KIT p-7Y-KIT p-7Y-KIT SHP2SFKsp-KITsSCF dimerp-KITLCK p-7Y-KIT YES1GRB2SOS1p-KIT complexKITLG-1FYNp-KIT SOCS1GRAP YES1LYNp21 RASGDPp-Y142,Y160,Y174-VAV1 GRB10 PISH2B2 GRB2-1 p-Y546,Y584-PTPN11 p-7Y-KIT Grb2SOSp-c-Kit/p-APSp-c-Kit complexGRAP2 p-Y705-STAT3 KITLG-1LCK GTPGAB2 SHP-1p-c-Kit complexPTPRUSRC-1 LYNAPS dimerp-7Y-KIT YES1p-JAK2SFKsp-KIT complexKITLG-1KITLG-1YES1p-Y546,Y584-PTPN11 p-Y-GAB2 TEC SRC-1 p-7Y-KIT PIK3CA GTPLYNSRC-1 KITsSCF dimerKITKRASp-7Y-KIT SRC-1 YES1GDPJAK2 STAT3 SFKsp-KIT complexSOCS6p-c-KitsSCF dimerp-c-Kitp-S741,S746-KIT KITLG-1LYNKITLG-1FYNKITLG-1FYNLCK p-Y694-STAT5A p-Y699-STAT5B SRC-1 YES1ADPRAC1-GDPKIT YES1p-Y546,Y584-PTPN11 FYNp-7Y-KIT FER KITLG-1GRB2SOS1SRC-1 SRC-1 p-JAK2SFKsp-KIT complexSTATsPRKCA KITLG-1FYNp-STAT dimersKITLG-1p-Y701-STAT1-1 GTP SFKsp-8Y-KITsSCF dimerp-8Y-KITSOS1 p-7Y-KIT PI3K alphaKITLG-1KITLG-1HRASADPPIKITLG-1Adapter proteinsp-KIT complexEndopeptidases for SCF processingLCK PIP3 activates AKT signalingSTAT5B p-SHP2p-KIT complexGRB2-1 LYNp-7Y-KIT Tyrosine kinasesp-KIT complexp-7Y-KITsSCF dimerp-7Y-KITRAC1-GTPKITLG-1GRB2-1 PTPROKITYES1SRC-1 GDP GRB2-1 GRB2-1 p-7Y-KIT KITLG-1KITLG-1KRASLCK KITLG-1LNKp-7Y-KITsSCF dimerp-7Y-KITLYNPRKCASH2B3SRC-1 KITLG-1p21 RASGTPLCK HRASADPp-7Y-KIT Src family tyrosine kinases FYNCHEK1 CBLGrb2/p-APSp-c-Kit complexLCK KITLG-1RAC1 YES1ATPp-8Y-KIT FYNPIK3CA ADPSOS1 ADPATPFYNKITLG-1VAV1p-7Y-KIT LYNSRC-1 sSCF dimerLYNp-7Y-KIT GDP ATPPIK3CA YES1LCK p-Y1007-JAK2 GAB2SOCS6 SOCS1p-KIT complexFYNATPPTPN6p-Y-GAB2 YES1PTPN11SRC-1 PI3Kp-KITsSCF dimerp-KITNRAS LYNGTP p-Y546,Y584-PTPN11 LCK CBL LCK PTPN6 KITLG-1YES1Adapter proteinsGRB7 p-Y701-STAT1-1 p-7Y-KIT SH2B3 p-7Y-KIT p-APS dimerp-KIT complexKIT LCK KITLG-1ATPSRC-1 p-7Y-KIT LCK KITsSCF dimerSRC-1 p-Y705-STAT3 SRC-1 p-Y705-STAT3 RAC1 p-7Y-KIT KITLG-1p-7Y-KIT PTPRUP13KpRAF/MAP kinase cascadeSTATsKITLG-1FYNLYNJAK2SOCS6p-Y1007-JAK2 KITLG-1GRB2p-SHP2p-KIT complexKIT GRB2-1LCK 21, 34


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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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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 complexComplexREACT_111421 (Reactome)
Adapter proteinsProteinREACT_111747 (Reactome)
CBL

Grb2/p-APS

p-c-Kit complex
ComplexREACT_111310 (Reactome)
CBL ProteinP22681 (Uniprot-TrEMBL)
CBLProteinP22681 (Uniprot-TrEMBL)
CHEK1 ProteinO14757 (Uniprot-TrEMBL)
Endopeptidases for SCF processingProteinREACT_111360 (Reactome)