Signaling by SCF-KIT (Homo sapiens)

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18, 35, 44, 56, 64...44, 61, 642, 16, 44, 454824, 29, 512929, 516, 25, 33, 34, 50...5, 33, 60, 64232712, 19, 46, 538, 32, 33, 65, 689, 31, 4143415215, 54464, 14, 40, 4833, 62, 6821, 30, 337, 11, 17, 3728, 4838, 58412942, 5826, 434337, 5520, 33, 34, 49, 681, 3, 7, 13, 22...47, 59SFKsp-KIT complex sSCF dimer p-APS dimerp-KIT complex Src family tyrosine kinases SFKsp-KIT complex SFKsp-KIT complex Src family tyrosine kinases Src family tyrosine kinases Src family tyrosine kinases APS dimer STATs SFKsp-KIT complex Src family tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT JAK2SFKSp-KIT complex cytosolp-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex sSCF dimer sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT RAC1-GTP sSCF dimer sSCF dimer SFKsp-KIT complex Tyrosine kinasesp-KIT complex sSCF dimer SFKsp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT GAB2GRB2p-SHP2p-KIT complex p-JAK2SFKsp-KIT complex P13KpsSCF dimer sSCF dimer Src family tyrosine kinases PI3K alpha sSCF dimer sSCF dimer sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-8Y-KITsSCF dimerp-8Y-KIT p-SHP2p-KIT complex Src family tyrosine kinases p-STAT dimers GRB2p-SHP2p-KIT complex sSCF dimer p21 RAS p-8Y-KITsSCF dimerp-8Y-KIT p-STATs pSFKsp-KIT complex SHP2SFKsp-KITsSCF dimerp-KIT sSCF dimer Src family tyrosine kinases p21 RASGTP PI3Kp-KITsSCF dimerp-KIT p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases APS dimerp-c-KitSFKs complex Src family tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT p-VAV1PIP3 sSCF dimer GRB2p-SHP2p-KIT complex sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT PI3K alpha SOCS1p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases sSCF dimer GRB2SOS1 KITsSCF dimerKIT nucleoplasmsSCF dimer sSCF dimer GRB2SOS1p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer p-JAK2SFKsp-KIT complexSTATs sSCF dimer GRB2p-SHP2p-KIT complex p-STAT dimer p-APS dimer SFKsp-KIT complex Src family tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT Adapter proteins p-JAK2SFKsp-KIT complexp-STAT dimers p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases p-SHP2p-KIT complex KITsSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT CBLGrb2/p-APSp-c-Kit complex SHP-1p-c-Kit complex GRB2SOS1 p-JAK2SFKsp-KIT complexp-STATs GRB2SOS1p-KIT complex p-APS dimerp-KIT complex p-STATs sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex PI3K alpha APS dimer p21 RAS SFKsp-KIT complex RAC1-GDP sSCF dimer GRB2p-SHP2p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer PTPROKIT p-7Y-KITsSCF dimerp-7Y-KIT p-SHP2p-KIT complex p-KIT Src family tyrosine kinases SFKsp-KIT complex sSCF dimer p21 RASGDP Grb2SOSp-c-Kit/p-APSp-c-Kit complex Src family tyrosine kinases Tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT p-SHP2p-KIT complex sSCF dimer LNKp-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer SOCS6p-c-KitsSCF dimerp-c-Kit p-APS dimer SFKsp-KIT complex GRB2SOS1 Adapter proteinsp-KIT complex p-STATs sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases p-SHP2p-KIT complex LCK p-7Y-KIT SFKsp-8Y-KITsSCF dimerp-8Y-KITYES1p-Y694-STAT5A ATPPIK3CA SOCS1SRC-1 GAB2GRB2p-SHP2p-KIT complexGRB2SOS1p-Y701-STAT1-1 sSCF dimerLYNKITLG-1KITLG-1p-Y1007-JAK2 p-JAK2SFKsp-KIT complexSTATsNRAS KITLG-1YES1VAV1FYNp-Y701-STAT1-1 GDP FER KIT LCK PIRAF/MAP kinase cascadeLYNAPS dimerp-c-KitSFKs complexp-Y1007-JAK2 p-7Y-KIT KITLG-1PTPN6 p-Y629-SH2B2 ATPGRB2-1p-Y1007-JAK2 SRC-1 LCK SH2B2 SOCS1p-KIT complexSTATsFYNGAB2 p-Y546,Y584-PTPN11 FYNPTPN11FYNKITLG-1YES1KITLG-1p-7Y-KIT p-7Y-KIT p-7Y-KIT KITLG-1SRC-1 HRASPI3Kp-KITsSCF dimerp-KITpp-Y1007-JAK2 ATPp-7Y-KIT KITLG-1p-JAK2SFKsp-KIT complexp-STATsAPS dimerGRB10 SRC-1 SRC-1 GDPYES1LNKp-7Y-KITsSCF dimerp-7Y-KITFYNGRB2-1 SH2B3 GRB2-1 KITLG-1p-7Y-KIT Adapter proteinsp-KIT complexFYNp-Y705-STAT3 PTPRUp-VAV1PIP3GRAP2 KITLG-1SH2B2 KITLG-1p-7Y-KIT SOCS6p-c-KitsSCF dimerp-c-KitKITLG-1Adapter proteinsp-Y694-STAT5A LCK YES1RAC1 ADPPRKCAPTPRULYNp-APS dimerp-KIT complexp-7Y-KIT GRB2-1 FYNp-7Y-KIT LCK KITsSCF dimerFYNp-7Y-KIT p-Y546,Y584-PTPN11 CHEK1 LYNSRC-1 p-7Y-KIT p-7Y-KIT p-SHP2p-KIT complexLYNKIT p21 RASGDPSRC-1 LYNFYNKITLG-1JAK2STAT5A PRKCA KITLG-1ADPGRB7 STAT3 Endopeptidases for SCF processingADPSOCS6 JAK2SFKSp-KIT complexYES1p-JAK2SFKsp-KIT complexp-STAT dimersp-STAT dimersLYNFYNADPATPPTPROKITFYNp-7Y-KIT SHP2SFKsp-KITsSCF dimerp-KITSRC-1 Tyrosine kinasesp-KIT complexp-7Y-KITsSCF dimerp-7Y-KITRAC1 LYNLYNKITLG-1p-KIT LCK ATPKITLG-1LCK p-Y694-STAT5A RAC1-GTPATPGRB2SOS1p-KIT complexTEC KITLG-1SOCS1 KIT GRB2-1 PIP3 activates AKT signalingp-7Y-KIT LCK KITLG-1KITLG-1YES1p-Y705-STAT3 STAT1 KITLG-1SOS1 JAK2 SRC-1 GRB2-1 KITLG-1GTPSRC-1 CBLGrb2/p-APSp-c-Kit complexp-Y629-SH2B2 FYNLYNRAC1-GDPGTP KITLG-1SRC-1 SOS1 LCK p21 RASGTPYES1LCK PIK3CA P13Kpp-7Y-KIT p-Y-GAB2 LYNFES NRAS YES1GDP KITLG-1SHP-1p-c-Kit complexp-S741,S746-KIT ADPTyrosine kinasesGrb2SOSp-c-Kit/p-APSp-c-Kit complexYES1LCK GDPFYNp-7Y-KIT LCK Src family tyrosine kinases p-8Y-KIT KITLG-1CBL PIKITLG-1GAB2PISRC-1 p-Y705-STAT3 LYNKITLG-1SFKsp-KIT complexADPKRASp-Y546,Y584-PTPN11 GRB2-1 FYNYES1KITLG-1p-Y701-STAT1-1 PI3K alphaSOCS6KITLG-1p-JAK2SFKsp-KIT complexPIK3CA KITLG-1p-Y546,Y584-PTPN11 FYNGTPLYNp-Y142,Y160,Y174-VAV1 HRASGRB2p-SHP2p-KIT complexKRASp-7Y-KIT YES1CBLYES1PTPN6LCK FYNp-7Y-KIT GRAP p-Y699-STAT5B SRC-1 SH2B3SRC-1 ATPKITYES1KITsSCF dimerKITp-7Y-KIT LYNSRC-1 YES1KITLG-1LYNp-Y699-STAT5B LYNp-Y699-STAT5B ADPSRC-1 SOS1 GRB2-1 LCK ADPp-7Y-KIT p-7Y-KIT LCK STAT5B PTPN11 p-7Y-KIT p-7Y-KIT GTP LCK p-Y546,Y584-PTPN11 KITLG-1p-Y-GAB2 YES110, 36


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:

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  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


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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


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


SFKs complex
ComplexREACT_111288 (Reactome)
APS dimerComplexREACT_111367 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
Adapter proteins p-KIT complexComplexREACT_111421 (Reactome)
Adapter proteinsProteinREACT_111747 (Reactome)


p-c-Kit complex
ComplexREACT_111310 (Reactome)
CBL ProteinP22681 (Uniprot-TrEMBL)
CBLProteinP22681 (Uniprot-TrEMBL)
CHEK1 ProteinO14757 (Uniprot-TrEMBL)
Endopeptidases for SCF processingProteinREACT_111360 (Reactome)
FER ProteinP16591 (Uniprot-TrEMBL)
FES ProteinP07332 (Uniprot-TrEMBL)
FYNProteinP06241 (Uniprot-TrEMBL)


p-KIT complex
ComplexREACT_111599 (Reactome)
GAB2 ProteinQ9UQC2 (Uniprot-TrEMBL)
GAB2ProteinQ9UQC2 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRAP ProteinQ13588 (Uniprot-TrEMBL)
GRAP2 ProteinO75791 (Uniprot-TrEMBL)
GRB10 ProteinQ13322 (Uniprot-TrEMBL)


p-KIT complex
ComplexREACT_111435 (Reactome)
GRB2 SOS1ComplexREACT_4435 (Reactome)


p-KIT complex
ComplexREACT_111665 (Reactome)
GRB2-1 Protein