Kit receptor signaling pathway (Homo sapiens)

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RPS6KA1RPS6KA3PAKT1P6, 88, 139, 164, 278...230, 443528396268, 443396205, 422, 517268, 443385, 396314, 434288, 451, 460105, 216, 317166, 443186, 273, 582164, 175, 183120, 128, 138, 186, 391164, 17546017998, 186235, 254291, 30541, 120, 234, 389, 530294, 442120, 300, 43213, 120, 235, 530, 553108, 528443235, 25443, 291288, 33248, 477, 53041, 120, 235, 340, 53041, 114, 120, 300, 389...114, 16419, 44319, 443107, 437333, 443254, 29169, 186, 237, 288120, 300, 305, 44316441, 505450, 549120, 300, 38656, 88, 108, 120, 254...206, 300, 57531, 41, 7441, 120, 235, 300, 574...183, 282120, 186, 288, 291, 490...41, 527, 573Kit Receptor Signal Transduction PathwayPhospholipase DCYNUDOK1PCRK120, 162, 175, 186P183, 282EP300KITLGKITVAV1P314, 406FOSGAB2TECP88, 333BCL2MAP2K2PGRB7128, 335, 527SHC1SH2B2P13, 314, 528KITFYNUbCRKLSNAI2JAK2P584TBX2STAT5BPIK3R2SOCS1PLCG1P6, 120, 158, 291, 450SNAI1BTKPGRB10218, 450LYNMATKPTPN6KITCBLPSOCS6314, 463, 583RPS6KITLGMTORP64SOS1RAF1P145, 186MAP2K1P128, 139, 527INPP5DSTAT3STAT3P210, 264STAT1MAPK1P6, 31, 35, 88, 139...FOXO3ASTAT1P314, 460, 534GRB2MAPK3P6, 31, 35, 88, 139...PTPN11P88RPS6KB1P35, 64, 534STAT5ASTAT5BSTAT5AP44, 442JUNBPRKCABADPRKCB1MAPK8MAPK8PMAPK1464, 88, 377PPIK3R1SRCP6, 59, 64, 88, 570...P108, 52758, 120, 128MITFSTAT5AHRASGTP107, 294451RPS6KA1RPS6KA3RPS6KB1179MAPK1MAPK3CYNUCYNUCYNUCYNUEnzyme complexInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationProteinmRNAProteinReceptorLigandDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavage


Kit is a cytokine receptor that belongs to the type III receptor tyrosine kinase family. It is structurally similar to platelet-derived growth factor recpetors (PDGFRs), colony stimulating factor-1 receptor and fms-like tyrosine kinase. Kit signaling is plays important role in a number of physiological processes including erythropoiesis, lymphopoiesis, mast cell development and function, megakaryopoiesis, gametogenesis and melanogenesis. Sequence alterations in the c-kit gene are found to be associated with different cancers including hematopoietic malignancies, gastrointestinal stromal tumors, germ cell tumors, small-cell lung cancer and pancreatic cancer.

The primary ligand for kit receptor is stem cell factor (SCF). It is also known as Kit ligand, steel factor or mast cell growth factor. SCF is a glycosylated, non-covalent homodimer. Alternative splicing and proteolytic cleavage results in soluble and membrane bound forms of the protein. that binds to two KIT monomers.

Binding of SCF to KIT results in the dimerization of the receptor and its autophsphorylation. The residues that are known to get phosphorylated upon ligand binding include Tyr568, Tyr570, Tyr703, Tyr721, Tyr730, Tyr823, Tyr 900 and Tyr936. SIgnaling events downstream of the KIT receptor are well studied. Among the signaling cascades that are activated are the Ras/Raf/MEK/MAPK and the PI3K/AKT/RPS6K pathways. KIT stimulation is also known to activate the JAK/STAT and PLC/PKC signaling pathways. Among the other key proteins that are regulated by KIT are the kinases BTK, TEC, LYN, SRC, FYN and JNK.

Regulation of KIT receptor tyrosine kinase occurs through many mechanisms. Activated KIT receptors are degraded via CBL, a E3 ubiquitin-protein ligase. CBL induces the degradation of the receptor via the proteasome or lysosome. KIT can also be dephosphorylated and inactivated by the protein tyrosine phsophatase Shp1. Also, activation of protein kinase C results in a negative feedback loop, wherein it phosphorylates specific serine residues leading to the inactivation of KIT.

NetPath ( is a collaborative effort between PandeyLab at Johns Hopkins University ( and Institute of Bioinformatics ( This version of the pathway is available at NetSlim ( If you use this pathway, please cite the NetPath website.

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108331view21:17, 6 December 2019L DupuisConverted interactions to graphical lines in legend
78799view18:30, 30 January 2015EgonwCopied Entrez IDs for STAT5B and STAT5A from nodes elsewhere in the pathway.
78539view10:30, 7 January 2015MaintBotadded missing graphIds
72102view21:45, 24 October 2013Mkutmonadded datasource for "GAB2", "FYN", "CRKL" and "GRB2"
68995view17:44, 8 July 2013MaintBotUpdated to 2013 gpml schema
67427view11:00, 26 June 2013DdiglesOntology Term : 'Stem Cell Factor signaling pathway' added !
47975view14:28, 23 April 2012NetPathModified description
44883view10:10, 6 October 2011MartijnVanIerselOntology Term : 'cytokine mediated signaling pathway' added !
44603view21:15, 21 September 2011KhanspersUpdating content to NetSlim
44112view20:36, 24 August 2011KhanspersReverted to version '23:42, 1 March 2011' by Khanspers
44033view23:13, 22 August 2011KhanspersModified description
44032view23:12, 22 August 2011KhanspersUpdating pathway from NetSlim
41172view23:42, 1 March 2011MaintBotRemoved redundant pathway information and comments
35649view21:40, 12 February 2010KhanspersModified description
21319view11:31, 14 November 2008MaintBot[[Pathway:Homo sapiens:Kit-Receptor NetPath 6]] moved to [[Pathway:WP304]]: Moved to stable identifier
13001view11:01, 17 May 2008MaintBotSticky edges patch by Sjoerd
8230view13:46, 7 January 2008MaintBot[[Pathway:Human:Kit-Receptor NetPath 6]] moved to [[Pathway:Homo sapiens:Kit-Receptor NetPath 6]]: Renaming species
7735view16:14, 18 December 2007MaintBotfixed category names
7271view12:41, 4 November 2007MaintBotAdded categories to GPML
6347view22:18, 22 May 2007A.Pandeygpml file for [[Human:Kit-Receptor_NetPath_6]]

External references


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NameTypeDatabase referenceComment
AKT1GeneProduct207 (Entrez Gene)
BADGeneProduct572 (Entrez Gene)
BCL2Rna596 (Entrez Gene)
BTKGeneProduct695 (Entrez Gene)
CBLGeneProduct867 (Entrez Gene)
CRKGeneProduct1398 (Entrez Gene)
DOK1GeneProduct1796 (Entrez Gene)
EP300GeneProduct2033 (Entrez Gene)
FOSRna2353 (Entrez Gene)
FOXO3AGeneProduct2309 (Entrez Gene)
GRB10GeneProduct2887 (Entrez Gene)
GRB7GeneProduct2886 (Entrez Gene)
HRASGeneProduct3265 (Entrez Gene)
INPP5DGeneProduct3635 (Entrez Gene)
JAK2GeneProduct3717 (Entrez Gene)
JUNBRna3726 (Entrez Gene)
KITGeneProduct3815 (Entrez Gene)
KITLGGeneProduct4254 (Entrez Gene)
LYNGeneProduct4067 (Entrez Gene)
LigandGeneProduct7040 (Entrez Gene)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAPK14GeneProduct1432 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MAPK8GeneProduct5599 (Entrez Gene)
MATKGeneProduct4145 (Entrez Gene)
MITFGeneProduct4286 (Entrez Gene)
MTORGeneProduct4137 (Entrez Gene)
PIK3R1GeneProduct5295 (Entrez Gene)
PIK3R2GeneProduct5296 (Entrez Gene)
PLCG1GeneProduct5335 (Entrez Gene)
PRKCAGeneProduct5578 (Entrez Gene)
PRKCB1GeneProduct5579 (Entrez Gene)
PTPN11GeneProduct5781 (Entrez Gene)
PTPN6GeneProduct5777 (Entrez Gene)
ProteinProtein5894 (Entrez Gene)
RAF1GeneProduct5894 (Entrez Gene)
RPS6GeneProduct6194 (Entrez Gene)
RPS6KA1GeneProduct6195 (Entrez Gene)
RPS6KA3GeneProduct6197 (Entrez Gene)
RPS6KB1GeneProduct6198 (Entrez Gene)
ReceptorGeneProduct7040 (Entrez Gene)
SH2B2GeneProduct10603 (Entrez Gene)
SHC1GeneProduct6464 (Entrez Gene)
SNAI1Rna6615 (Entrez Gene)
SNAI2Rna6591 (Entrez Gene)
SOCS1GeneProduct8651 (Entrez Gene)
SOCS6GeneProduct9306 (Entrez Gene)
SOS1GeneProduct6654 (Entrez Gene)
SRCGeneProduct6714 (Entrez Gene)
STAT1GeneProduct6772 (Entrez Gene)
STAT3GeneProduct6774 (Entrez Gene)
STAT5AGeneProduct6776 (Entrez Gene)
STAT5AGeneProductSTAT5A (Entrez Gene)
STAT5BGeneProduct6777 (Entrez Gene)
STAT5BGeneProductSTAT5B (Entrez Gene)
TBX2Rna6909 (Entrez Gene)
TECGeneProduct7006 (Entrez Gene)
VAV1GeneProduct7409 (Entrez Gene)

Annotated Interactions

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