KIT (gene)

Mammalian protein and protein-coding gene

KIT

| Available structures

PDB| Ortholog search: PDBe RCSB
| List of PDB id codes

4U0I, 1PKG, 1T45, 1T46, 2E9W, 2EC8, 2VIF, 3G0E, 3G0F, 4HVS, 4K94, 4K9E, 4PGZ, 2IUH

Identifiers
Aliases| KIT, C-Kit, CD117, PBT, SCFR, KIT proto-oncogene receptor tyrosine kinase, MASTC, KIT proto-oncogene, receptor tyrosine kinase
External IDs| OMIM: 164920; MGI: 96677; HomoloGene: 187; GeneCards: KIT; OMA:KIT - orthologs
| Gene location (Human)

Chr.| Chromosome 4 (human)[1]

Band| 4q12| Start| 54,657,918 bp[1]
End| 54,740,715 bp[1]
| Gene location (Mouse)

Chr.| Chromosome 5 (mouse)[2]

Band| 5 C3.3|5 39.55 cM| Start| 75,735,576 bp[2]
End| 75,817,382 bp[2]
| RNA expression pattern

Bgee| | Human| Mouse (ortholog)

|

| Top expressed in

* lateral nuclear group of thalamus

* secondary oocyte

* skin of thigh

* epithelium of lactiferous gland

* gonad

* lactiferous duct

* cardia

* parotid gland

* skin of hip

* visceral pleura

| Top expressed in

* lobe of cerebellum

* cerebellar vermis

* secondary oocyte

* primary oocyte

* zygote

* gastrula

* dermis

* liver parenchyma

* muscle layer of urethra

* decidua

More reference expression data
BioGPS| | n/a

| Gene ontology

Molecular function|

* stem cell factor receptor activity
* kinase activity
* transmembrane receptor protein tyrosine kinase activity
* ATP binding
* cytokine binding
* protein kinase activity
* metal ion binding
* transferase activity
* protein homodimerization activity
* protease binding
* protein binding
* protein tyrosine kinase activity
* nucleotide binding
* phosphatidylinositol-4,5-bisphosphate 3-kinase activity
* receptor tyrosine kinase
* transmembrane signaling receptor activity
* SH2 domain binding

Cellular component|

* cytoplasm
* membrane
* cell-cell junction
* cytoplasmic side of plasma membrane
* cell surface
* integral component of membrane
* acrosomal vesicle
* external side of plasma membrane
* mast cell granule
* extracellular space
* plasma membrane
* integral component of plasma membrane
* receptor complex

Biological process|

* melanocyte migration
* myeloid progenitor cell differentiation
* positive regulation of MAP kinase activity
* glycosphingolipid metabolic process
* positive regulation of phospholipase C activity
* hematopoietic stem cell migration
* stem cell population maintenance
* protein phosphorylation
* T cell differentiation
* spermatogenesis
* cell chemotaxis
* developmental pigmentation
* melanocyte differentiation
* positive regulation of Notch signaling pathway
* lamellipodium assembly
* cytokine-mediated signaling pathway
* transmembrane receptor protein tyrosine kinase signaling pathway
* melanocyte adhesion
* lymphoid progenitor cell differentiation
* spermatid development
* erythrocyte differentiation
* negative regulation of programmed cell death
* protein autophosphorylation
* mast cell degranulation
* inflammatory response
* positive regulation of MAPK cascade
* myeloid leukocyte differentiation
* male gonad development
* phosphorylation
* positive regulation of DNA-binding transcription factor activity
* epithelial cell proliferation
* stem cell differentiation
* detection of mechanical stimulus involved in sensory perception of sound
* regulation of cell shape
* ovarian follicle development
* ectopic germ cell programmed cell death
* pigmentation
* Fc receptor signaling pathway
* response to radiation
* mast cell cytokine production
* positive regulation of receptor signaling pathway via JAK-STAT
* dendritic cell cytokine production
* visual learning
* actin cytoskeleton reorganization
* megakaryocyte development
* intracellular signal transduction
* somatic stem cell population maintenance
* erythropoietin-mediated signaling pathway
* Kit signaling pathway
* positive regulation of cell migration
* somatic stem cell division
* mast cell chemotaxis
* MAPK cascade
* positive regulation of phosphatidylinositol 3-kinase activity
* positive regulation of pseudopodium assembly
* positive regulation of gene expression
* positive regulation of long-term neuronal synaptic plasticity
* regulation of cell population proliferation
* cellular response to thyroid hormone stimulus
* positive regulation of cell population proliferation
* embryonic hemopoiesis
* regulation of developmental pigmentation
* positive regulation of phosphatidylinositol 3-kinase signaling
* peptidyl-tyrosine phosphorylation
* mast cell differentiation
* digestive tract development
* immature B cell differentiation
* germ cell migration
* signal transduction
* mast cell proliferation
* positive regulation of vascular associated smooth muscle cell differentiation
* phosphatidylinositol phosphate biosynthetic process
* regulation of transcription by RNA polymerase II
* positive regulation of tyrosine phosphorylation of STAT protein
* tongue development
* response to cadmium ion
* positive regulation of pyloric antrum smooth muscle contraction
* regulation of bile acid metabolic process
* positive regulation of small intestine smooth muscle contraction
* positive regulation of colon smooth muscle contraction
* positive regulation of protein kinase B signaling
* hemopoiesis
* negative regulation of signal transduction
* cell differentiation
* negative regulation of apoptotic process
* positive regulation of ERK1 and ERK2 cascade
* hematopoietic progenitor cell differentiation
* B cell differentiation

Sources:Amigo / QuickGO
| Orthologs

Species| Human| Mouse
Entrez| |

3815

16590

Ensembl| |

ENSG00000157404

ENSMUSG00000005672

UniProt| |

P10721

P05532

RefSeq (mRNA)| |

NM_000222
NM_001093772

NM_001122733
NM_021099

RefSeq (protein)| |

NP_000213
NP_001087241

NP_001116205
NP_066922

Location (UCSC)| Chr 4: 54.66 – 54.74 Mb| Chr 5: 75.74 – 75.82 Mb
PubMed search| [3]| [4]
Wikidata
| View/Edit Human| View/Edit Mouse

|

Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR).[5] Multiple transcript variants encoding different isoforms have been found for this gene.[6][7] KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.[8]

## Function

[edit]

KIT is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of cancer.[9] KIT is a receptor tyrosine kinase type III, which binds to stem cell factor, also known as "steel factor" or "c-kit ligand". When this receptor binds to stem cell factor (SCF) it forms a dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell.[10] After activation, the receptor is ubiquitinated to mark it for transport to a lysosome and eventual destruction. Signaling through KIT plays a role in cell survival, proliferation, and differentiation. For instance, KIT signaling is required for melanocyte survival, and it is also involved in haematopoiesis and gametogenesis.[11]

## Structure

[edit]

Like other members of the receptor tyrosine kinase III family, KIT consists of an extracellular domain, a transmembrane domain, a juxtamembrane domain, and an intracellular tyrosine kinase domain. The extracellular domain is composed of five immunoglobulin-like domains, and the protein kinase domain is interrupted by a hydrophilic insert sequence of about 80 amino acids. The ligand stem cell factor binds via the second and third immunoglobulin domains.[12][10][13]

## Cell surface marker

[edit]

Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell. KIT is an important cell surface marker used to identify certain types of hematopoietic (blood) progenitors in the bone marrow. To be specific, hematopoietic stem cells (HSC), multipotent progenitors (MPP), and common myeloid progenitors (CMP) express high levels of KIT. Common lymphoid progenitors (CLP) express low surface levels of KIT. KIT also identifies the earliest thymocyte progenitors in the thymus—early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit. It is also a marker for mouse prostate stem cells.[14] In addition, mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express KIT. In humans, expression of c-kit in helper-like innate lymphoid cells (ILCs) which lack the expression of CRTH2 (CD294) is used to mark the ILC3 population.[15]

CD117/c-KIT is expressed not only by bone marrow-derived stem cells, but also by those found in other adult organs, such as the prostate, liver, and heart, suggesting that SCF/c-KIT signaling pathways may contribute to stemness in some organs. Additionally, c-KIT has been associated with numerous biological processes in other cell types. For example, c-KIT signaling, has been shown to regulate oogenesis, folliculogenesis, and spermatogenesis, playing important roles in female and male fertility.[16]

## Mobilization

[edit]

Hematopoietic progenitor cells are normally present in the blood at low levels. Mobilization is the process by which progenitors are made to migrate from the bone marrow into the bloodstream, thus increasing their numbers in the blood. Mobilization is used clinically as a source of hematopoietic stem cells for hematopoietic stem cell transplantation (HSCT). Signaling through KIT has been implicated in mobilization. At the current time, G-CSF is the main drug used for mobilization; it indirectly activates KIT. Plerixafor (an antagonist of CXCR4-SDF1) in combination with G-CSF, is also being used for mobilization of hematopoietic progenitor cells. Direct KIT agonists are currently being developed as mobilization agents.

## Role in cancer

[edit]

Activating mutations in this gene are associated with gastrointestinal stromal tumors, testicular seminoma, mast cell disease, melanoma, acute myeloid leukemia, while inactivating mutations are associated with the genetic defect piebaldism.[6]

c-KIT plays an important role in regulating many mechanisms leading to tumor formation and progression of carcinomas. c-KIT has been proposed as a regulator of stemness in several cancers. Its expression has been linked to cancer stemness in ovarian cancer cells, colon cancer cells, non-small cell lung cancer cells, and prostate cancer cells. c-KIT has also been linked to the epithelial-mesenchymal transition (EMT), which is important for tumor aggressiveness and metastatic potential. Ectopic expression of c-KIT and EMT have been linked in denoid cystic carcinoma of the salivary gland, thymic carcinomas, ovarian cancer cells, and prostate cancer cells. Several lines of evidence suggest that SCF/c-KIT signaling plays an important role in the tumor microenvironment. For example, in mice high levels of c-KIT in mast cells as well as its presence in the tumor microenvironment promote angiogenesis, leading to increased tumor growth and metastasis.[16]

### Anti-KIT therapies

[edit]

KIT is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer.[17] Seminomas, a subtype of testicular germ cell tumors, frequently have activating mutations in exon 17 of KIT. In addition, the gene encoding KIT is frequently overexpressed and amplified in this tumor type, most commonly occurring as a single gene amplicon.[18] Mutations of KIT have also been implicated in leukemia, a cancer of hematopoietic progenitors, melanoma, mast cell disease, and gastrointestinal stromal tumors (GISTs). The efficacy of imatinib (trade name Gleevec), a KIT inhibitor, is determined by the mutation status of KIT:

When the mutation has occurred in exon 11 (as is the case many times in GISTs), the tumors are responsive to imatinib. However, if the mutation occurs in exon 17 (as is often the case in seminomas and leukemias), the receptor is not inhibited by imatinib. In those cases other inhibitors such as dasatinib Avapritinib or nilotinib can be used. Researchers investigated the dynamic behavior of wild type and mutant D816H KIT receptor, and emphasized the extended A-loop (EAL) region (805-850) by conducting computational analysis.[19] Their atomic investigation of mutant KIT receptor which emphasized on the EAL region provided a better insight into the understanding of the sunitinib resistance mechanism of the KIT receptor and could help to discover new therapeutics for KIT-based resistant tumor cells in GIST therapy.[19]

The preclinical agent, KTN0182A, is an anti-KIT, pyrrolobenzodiazepine (PBD)-containing antibody-drug conjugate which shows anti-tumor activity in vitro and in vivo against a range of tumor types.[20]

### Diagnostic relevance

[edit]

Antibodies to KIT are widely used in immunohistochemistry to help distinguish particular types of tumour in histological tissue sections. It is used primarily in the diagnosis of GISTs, which are positive for KIT, but negative for markers such as desmin and S-100, which are positive in smooth muscle and neural tumors, which have a similar appearance. In GISTs, KIT staining is typically cytoplasmic, with stronger accentuation along the cell membranes. KIT antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing seminomas from embryonal carcinomas.[21]

## Interactions

[edit]

KIT has been shown to interact with:

* APS,[22]
* BCR,[23]
* CD63,[24]
* CD81,[24]
* CD9,[24]
* CRK,[25]
* CRKL,[26][27]
* DOK1,[28]
* FES,[29]
* GRB10,[30]
* Grb2,[31][32][33]
* KITLG,[34][35]
* LNK,[36]
* LYN,[28][37]
* MATK,[38][39]
* MPDZ,[40]
* PIK3R1,[26][31][41]
* PTPN11,[42][43]
* PTPN6,[43][44]
* STAT1,[45]
* SOCS1,[31]
* SOCS6,[46]
* SRC,[47] and
* TEC.[48]

## See also

[edit]

* Cytokine receptor
* List of genes mutated in pigmented cutaneous lesions

## References

[edit]

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000157404 - Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000005672 - Ensembl, May 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, et al. (January 1997). "Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes". Genomics. 39 (2): 216–226. doi:10.1006/geno.1996.4482. PMID 9027509.
6. ^ a b "Entrez Gene: KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog".
7. ^ National Cancer Institute Dictionary of Cancer Terms. c-kit. Accessed October 13, 2014.
8. ^ Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, et al. (November 1987). "Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand". The EMBO Journal. 6 (11): 3341–3351. doi:10.1002/j.1460-2075.1987.tb02655.x. PMC 553789. PMID 2448137.
9. ^ Edling CE, Hallberg B (2007). "c-Kit--a hematopoietic cell essential receptor tyrosine kinase". The International Journal of Biochemistry & Cell Biology. 39 (11): 1995–1998. doi:10.1016/j.biocel.2006.12.005. PMID 17350321.
10. ^ a b Blume-Jensen P, Claesson-Welsh L, Siegbahn A, Zsebo KM, Westermark B, Heldin CH (December 1991). "Activation of the human c-kit product by ligand-induced dimerization mediates circular actin reorganization and chemotaxis". The EMBO Journal. 10 (13): 4121–4128. doi:10.1002/j.1460-2075.1991.tb04989.x. PMC 453162. PMID 1721869.
11. ^ Brooks S (2006). Studies of genetic variability at the KIT locus and white spotting patterns in the horse (Thesis). University of Kentucky Doctoral Dissertations. pp. 13–16.
12. ^ Roskoski R (December 2005). "Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor". Biochemical and Biophysical Research Communications. 338 (3): 1307–1315. doi:10.1016/j.bbrc.2005.09.150. PMID 16226710.
13. ^ Haase B, Brooks SA, Schlumbaum A, Azor PJ, Bailey E, Alaeddine F, et al. (November 2007). "Allelic heterogeneity at the equine KIT locus in dominant white (W) horses". PLOS Genetics. 3 (11): e195. doi:10.1371/journal.pgen.0030195. PMC 2065884. PMID 17997609.
14. ^ Leong KG, Wang BE, Johnson L, Gao WQ (December 2008). "Generation of a prostate from a single adult stem cell". Nature. 456 (7223): 804–808. Bibcode:2008Natur.456..804L. doi:10.1038/nature07427. PMID 18946470. S2CID 4410656.
15. ^ Vallentin B, Barlogis V, Piperoglou C, Cypowyj S, Zucchini N, Chéné M, et al. (October 2015). "Innate Lymphoid Cells in Cancer". Cancer Immunology Research. 3 (10): 1109–1114. doi:10.1158/2326-6066.CIR-15-0222. PMID 26438443.
16. ^ a b Sheikh E, Tran T, Vranic S, Levy A, Bonfil RD (April 2022). "Role and Significance of c-KIT Receptor Tyrosine Kinase in Cancer: A Review". Bosnian Journal of Basic Medical Sciences. 22 (5): 683–698. doi:10.17305/bjbms.2021.7399. PMC 9519160. PMID 35490363.
17. ^ Jean-Loup Huret. "KIT". Atlas of Genetics and Cytogenetics in Oncology and Haematology. Retrieved 2008-03-01.
18. ^ McIntyre A, Summersgill B, Grygalewicz B, Gillis AJ, Stoop J, van Gurp RJ, et al. (September 2005). "Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults". Cancer Research. 65 (18): 8085–8089. doi:10.1158/0008-5472.CAN-05-0471. PMID 16166280.
19. ^ a b Purohit R (2014). "Role of ELA region in auto-activation of mutant KIT receptor: a molecular dynamics simulation insight". Journal of Biomolecular Structure & Dynamics. 32 (7): 1033–1046. doi:10.1080/07391102.2013.803264. PMID 23782055. S2CID 5528573.
20. ^ KTN0182A, an Anti-KIT, Pyrrolobenzodiazepine (PBD)-Containing Antibody Drug Conjugate (ADC) Demonstrates Potent Antitumor Activity In Vitro and In Vivo Against a Broad Range of Tumor Types; Lubeski C, Kemp GC, Von Bulow CL, Howard PW, Hartley JA, Douville T, Wellbrock J, et al.; 11th Annual PEGS - The Essential Protein Engineering Summit, Boston, 2015 Archived October 30, 2015, at the Wayback Machine
21. ^ Leong AS, Cooper K, Leong FJ (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 149–151. ISBN 978-1-84110-100-2.
22. ^ Wollberg P, Lennartsson J, Gottfridsson E, Yoshimura A, Rönnstrand L (March 2003). "The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit". The Biochemical Journal. 370 (Pt 3): 1033–1038. doi:10.1042/BJ20020716. PMC 1223215. PMID 12444928.
23. ^ Hallek M, Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb HJ, et al. (July 1996). "Interaction of the receptor tyrosine kinase p145c-kit with the p210bcr/abl kinase in myeloid cells". British Journal of Haematology. 94 (1): 5–16. doi:10.1046/j.1365-2141.1996.6102053.x. PMID 8757502. S2CID 30033345.
24. ^ a b c Anzai N, Lee Y, Youn BS, Fukuda S, Kim YJ, Mantel C, et al. (June 2002). "C-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors". Blood. 99 (12): 4413–4421. doi:10.1182/blood.V99.12.4413. PMID 12036870.
25. ^ Lennartsson J, Wernstedt C, Engström U, Hellman U, Rönnstrand L (August 2003). "Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk". Experimental Cell Research. 288 (1): 110–118. doi:10.1016/S0014-4827(03)00206-4. PMID 12878163.
26. ^ a b van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M (November 2000). "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". Blood. 96 (10): 3406–3413. doi:10.1182/blood.V96.10.3406. hdl:1765/9530. PMID 11071635.
27. ^ Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, et al. (April 1997). "Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL)". The Journal of Biological Chemistry. 272 (15): 10248–10253. doi:10.1074/jbc.272.15.10248. PMID 9092574.
28. ^ a b Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD (April 2002). "Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling". The Journal of Biological Chemistry. 277 (16): 13732–13738. doi:10.1074/jbc.M200277200. PMID 11825908.
29. ^ Voisset E, Lopez S, Chaix A, Vita M, George C, Dubreuil P, et al. (February 2010). "FES kinase participates in KIT-ligand induced chemotaxis". Biochemical and Biophysical Research Communications. 393 (1): 174–178. doi:10.1016/j.bbrc.2010.01.116. PMID 20117079.
30. ^ Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (February 2002). "Role for the adaptor protein Grb10 in the activation of Akt". Molecular and Cellular Biology. 22 (4): 979–991. doi:10.1128/MCB.22.4.979-991.2002. PMC 134632. PMID 11809791.
31. ^ a b c De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (February 1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". The EMBO Journal. 18 (4): 904–915. doi:10.1093/emboj/18.4.904. PMC 1171183. PMID 10022833.
32. ^ Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L (July 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". The Biochemical Journal. 341 (1): 211–216. doi:10.1042/0264-6021:3410211. PMC 1220349. PMID 10377264.
33. ^ Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (May 1996). "Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway". The Journal of Biological Chemistry. 271 (21): 12129–12132. doi:10.1074/jbc.271.21.12129. PMID 8647802.
34. ^ Lev S, Yarden Y, Givol D (May 1992). "A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses". The Journal of Biological Chemistry. 267 (15): 10866–10873. doi:10.1016/S0021-9258(19)50098-9. PMID 1375232.
35. ^ Blechman JM, Lev S, Brizzi MF, Leitner O, Pegoraro L, Givol D, et al. (February 1993). "Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor". The Journal of Biological Chemistry. 268 (6): 4399–4406. doi:10.1016/S0021-9258(18)53623-1. PMID 7680037.
36. ^ Gueller S, Gery S, Nowak V, Liu L, Serve H, Koeffler HP (October 2008). "Adaptor protein Lnk associates with Tyr(568) in c-Kit" (PDF). The Biochemical Journal. 415 (2): 241–245. doi:10.1042/BJ20080102. PMID 18588518. S2CID 39310714.
37. ^ Linnekin D, DeBerry CS, Mou S (October 1997). "Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells". The Journal of Biological Chemistry. 272 (43): 27450–27455. doi:10.1074/jbc.272.43.27450. PMID 9341198.
38. ^ Jhun BH, Rivnay B, Price D, Avraham H (April 1995). "The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit". The Journal of Biological Chemistry. 270 (16): 9661–9666. doi:10.1074/jbc.270.16.9661. PMID 7536744.
39. ^ Price DJ, Rivnay B, Fu Y, Jiang S, Avraham S, Avraham H (February 1997). "Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes". The Journal of Biological Chemistry. 272 (9): 5915–5920. doi:10.1074/jbc.272.9.5915. PMID 9038210.
40. ^ Mancini A, Koch A, Stefan M, Niemann H, Tamura T (September 2000). "The direct association of the multiple PDZ domain containing proteins (MUPP-1) with the human c-Kit C-terminus is regulated by tyrosine kinase activity". FEBS Letters. 482 (1–2): 54–58. doi:10.1016/S0014-5793(00)02036-6. PMID 11018522. S2CID 40159587.
41. ^ Serve H, Hsu YC, Besmer P (February 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". The Journal of Biological Chemistry. 269 (8): 6026–6030. doi:10.1016/S0021-9258(17)37564-6. PMID 7509796.
42. ^ Tauchi T, Feng GS, Marshall MS, Shen R, Mantel C, Pawson T, et al. (October 1994). "The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells". The Journal of Biological Chemistry. 269 (40): 25206–25211. doi:10.1016/S0021-9258(17)31518-1. PMID 7523381.
43. ^ a b Kozlowski M, Larose L, Lee F, Le DM, Rottapel R, Siminovitch KA (April 1998). "SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain". Molecular and Cellular Biology. 18 (4): 2089–2099. doi:10.1128/MCB.18.4.2089. PMC 121439. PMID 9528781.
44. ^ Yi T, Ihle JN (June 1993). "Association of hematopoietic cell phosphatase with c-Kit after stimulation with c-Kit ligand". Molecular and Cellular Biology. 13 (6): 3350–3358. doi:10.1128/MCB.13.6.3350. PMC 359793. PMID 7684496.
45. ^ Deberry C, Mou S, Linnekin D (October 1997). "Stat1 associates with c-kit and is activated in response to stem cell factor". The Biochemical Journal. 327 (1): 73–80. doi:10.1042/bj3270073. PMC 1218765. PMID 9355737.
46. ^ Bayle J, Letard S, Frank R, Dubreuil P, De Sepulveda P (March 2004). "Suppressor of cytokine signaling 6 associates with KIT and regulates KIT receptor signaling". The Journal of Biological Chemistry. 279 (13): 12249–12259. doi:10.1074/jbc.M313381200. PMID 14707129.
47. ^ Lennartsson J, Blume-Jensen P, Hermanson M, Pontén E, Carlberg M, Rönnstrand L (September 1999). "Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction". Oncogene. 18 (40): 5546–5553. doi:10.1038/sj.onc.1202929. PMID 10523831.
48. ^ Tang B, Mano H, Yi T, Ihle JN (December 1994). "Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding". Molecular and Cellular Biology. 14 (12): 8432–8437. doi:10.1128/MCB.14.12.8432. PMC 359382. PMID 7526158.

## Further reading

[edit]

* Lennartsson J, Rönnstrand L (October 2012). "Stem cell factor receptor/c-Kit: from basic science to clinical implications". Physiological Reviews. 92 (4): 1619–1649. doi:10.1152/physrev.00046.2011. PMID 23073628.
* Lennartsson J, Rönnstrand L (February 2006). "The stem cell factor receptor/c-Kit as a drug target in cancer". Current Cancer Drug Targets. 6 (1): 65–75. doi:10.2174/156800906775471725. PMID 16475976.
* Rönnstrand L (October 2004). "Signal transduction via the stem cell factor receptor/c-Kit". Cellular and Molecular Life Sciences. 61 (19–20): 2535–2548. doi:10.1007/s00018-004-4189-6. PMID 15526160. S2CID 2602233.
* Linnekin D (October 1999). "Early signaling pathways activated by c-Kit in hematopoietic cells". The International Journal of Biochemistry & Cell Biology. 31 (10): 1053–1074. doi:10.1016/S1357-2725(99)00078-3. PMID 10582339.
* Canonico B, Felici C, Papa S (2001). "CD117". Journal of Biological Regulators and Homeostatic Agents. 15 (1): 90–94. PMID 11388751.
* Gupta R, Bain BJ, Knight CL (2002). "Cytogenetic and molecular genetic abnormalities in systemic mastocytosis". Acta Haematologica. 107 (2): 123–128. doi:10.1159/000046642. PMID 11919394. S2CID 20552257.
* Valent P, Ghannadan M, Hauswirth AW, Schernthaner GH, Sperr WR, Arock M (May 2002). "Signal transduction-associated and cell activation-linked antigens expressed in human mast cells". International Journal of Hematology. 75 (4): 357–362. doi:10.1007/BF02982124. PMID 12041664. S2CID 23033596.
* Sandberg AA, Bridge JA (May 2002). "Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. gastrointestinal stromal tumors". Cancer Genetics and Cytogenetics. 135 (1): 1–22. doi:10.1016/S0165-4608(02)00546-0. PMID 12072198.
* Kitamura Y, Hirotab S (December 2004). "Kit as a human oncogenic tyrosine kinase". Cellular and Molecular Life Sciences. 61 (23): 2924–2931. doi:10.1007/s00018-004-4273-y. PMID 15583854.
* Larizza L, Magnani I, Beghini A (February 2005). "The Kasumi-1 cell line: a t(8;21)-kit mutant model for acute myeloid leukemia". Leukemia & Lymphoma. 46 (2): 247–255. doi:10.1080/10428190400007565. PMID 15621809. S2CID 36086764.
* Miettinen M, Lasota J (September 2005). "KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation". Applied Immunohistochemistry & Molecular Morphology. 13 (3): 205–220. doi:10.1097/01.pai.0000173054.83414.22. PMID 16082245. S2CID 6912266.
* Lasota J, Miettinen M (May 2006). "KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)". Seminars in Diagnostic Pathology. 23 (2): 91–102. doi:10.1053/j.semdp.2006.08.006. PMID 17193822.
* Patnaik MM, Tefferi A, Pardanani A (August 2007). "Kit: molecule of interest for the diagnosis and treatment of mastocytosis and other neoplastic disorders". Current Cancer Drug Targets. 7 (5): 492–503. doi:10.2174/156800907781386614. PMID 17691909.
* Giebel LB, Strunk KM, Holmes SA, Spritz RA (November 1992). "Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene". Oncogene. 7 (11): 2207–2217. PMID 1279499.
* Spritz RA, Droetto S, Fukushima Y (November 1992). "Deletion of the KIT and PDGFRA genes in a patient with piebaldism". American Journal of Medical Genetics. 44 (4): 492–495. doi:10.1002/ajmg.1320440422. PMID 1279971.
* Spritz RA, Giebel LB, Holmes SA (February 1992). "Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism". American Journal of Human Genetics. 50 (2): 261–269. PMC 1682440. PMID 1370874.
* Duronio V, Welham MJ, Abraham S, Dryden P, Schrader JW (March 1992). "p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein". Proceedings of the National Academy of Sciences of the United States of America. 89 (5): 1587–1591. Bibcode:1992PNAS...89.1587D. doi:10.1073/pnas.89.5.1587. PMC 48497. PMID 1371879.
* André C, Martin E, Cornu F, Hu WX, Wang XP, Galibert F (April 1992). "Genomic organization of the human c-kit gene: evolution of the receptor tyrosine kinase subclass III". Oncogene. 7 (4): 685–691. PMID 1373482.
* Lev S, Yarden Y, Givol D (May 1992). "A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses". The Journal of Biological Chemistry. 267 (15): 10866–10873. doi:10.1016/S0021-9258(19)50098-9. PMID 1375232.
* Fleischman RA (June 1992). "Human piebald trait resulting from a dominant negative mutant allele of the c-kit membrane receptor gene". The Journal of Clinical Investigation. 89 (6): 1713–1717. doi:10.1172/JCI115772. PMC 295855. PMID 1376329.
* Vandenbark GR, deCastro CM, Taylor H, Dew-Knight S, Kaufman RE (July 1992). "Cloning and structural analysis of the human c-kit gene". Oncogene. 7 (7): 1259–1266. PMID 1377810.
* Alai M, Mui AL, Cutler RL, Bustelo XR, Barbacid M, Krystal G (September 1992). "Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells". The Journal of Biological Chemistry. 267 (25): 18021–18025. doi:10.1016/S0021-9258(19)37146-7. PMID 1381360.
* Ashman LK, Cambareri AC, To LB, Levinsky RJ, Juttner CA (July 1991). "Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow". Blood. 78 (1): 30–37. doi:10.1182/blood.V78.1.30.30. PMID 1712644.

## External links

[edit]

* Proto-Oncogene+Proteins+c-kit at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
* C-kit receptor entry in the public domain NCI Dictionary of Cancer Terms
* Human KIT genome location and KIT gene details page in the UCSC Genome Browser.

* v
* t
* e

PDB gallery

* 1pkg: Structure of a c-Kit Kinase Product Complex

* 1t45: STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE

* 1t46: STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE

* v
* t
* e

Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1–50|

* CD1
* a-c
* 1A
* 1B
* 1D
* 1E
* CD2
* CD3
* γ
* δ
* ε
* CD4
* CD5
* CD6
* CD7
* CD8
* a
* CD9
* CD10
* CD11
* a
* b
* c
* d
* CD13
* CD14
* CD15
* CD16
* A
* B
* CD18
* CD19
* CD20
* CD21
* CD22
* CD23
* CD24
* CD25
* CD26
* CD27
* CD28
* CD29
* CD30
* CD31
* CD32
* A
* B
* CD33
* CD34
* CD35
* CD36
* CD37
* CD38
* CD39
* CD40
* CD41
* CD42
* a
* b
* c
* d
* CD43
* CD44
* CD45
* CD46
* CD47
* CD48
* CD49
* a
* b
* c
* d
* e
* f
* CD50

51–100|

* CD51
* CD52
* CD53
* CD54
* CD55
* CD56
* CD57
* CD58
* CD59
* CD61
* CD62
* E
* L
* P
* CD63
* CD64
* A
* B
* C
* CD66
* a
* b
* c
* d
* e
* f
* CD68
* CD69
* CD70
* CD71
* CD72
* CD73
* CD74
* CD78
* CD79
* a
* b
* CD80
* CD81
* CD82
* CD83
* CD84
* CD85
* a
* d
* e
* h
* j
* k
* CD86
* CD87
* CD88
* CD89
* CD90
* CD91 \- CD92
* CD93
* CD94
* CD95
* CD96
* CD97
* CD98
* CD99
* CD100

101–150|

* CD101
* CD102
* CD103
* CD104
* CD105
* CD106
* CD107
* a
* b
* CD108
* CD109
* CD110
* CD111
* CD112
* CD113
* CD114
* CD115
* CD116
* CD117
* CD118
* CD119
* CD120
* a
* b
* CD121
* a
* b
* CD122
* CD123
* CD124
* CD125
* CD126
* CD127
* CD129
* CD130
* CD131
* CD132
* CD133
* CD134
* CD135
* CD136
* CD137
* CD138
* CD140b
* CD141
* CD142
* CD143
* CD144
* CD146
* CD147
* CD148
* CD150

151–200|

* CD151
* CD152
* CD153
* CD154
* CD155
* CD156
* a
* b
* c
* CD157
* CD158 (a
* d
* e
* i
* k)
* CD159
* a
* c
* CD160
* CD161
* CD162
* CD163
* CD164
* CD166
* CD167
* a
* b
* CD168
* CD169
* CD170
* CD171
* CD172
* a
* b
* g
* CD174
* CD177
* CD178
* CD179
* a
* b
* CD180
* CD181
* CD182
* CD183
* CD184
* CD185
* CD186
* CD191
* CD192
* CD193
* CD194
* CD195
* CD196
* CD197
* CDw198
* CDw199
* CD200

201–250|

* CD201
* CD202b
* CD204
* CD205
* CD206
* CD207
* CD208
* CD209
* CDw210
* a
* b
* CD212
* CD213a
* 1
* 2
* CD217
* CD218 (a
* b)
* CD220
* CD221
* CD222
* CD223
* CD224
* CD225
* CD226
* CD227
* CD228
* CD229
* CD230
* CD233
* CD234
* CD235
* a
* b
* CD236
* CD238
* CD239
* CD240CE
* CD240D
* CD241
* CD243
* CD244
* CD246
* CD247 \- CD248
* CD249

251–300|

* CD252
* CD253
* CD254
* CD256
* CD257
* CD258
* CD261
* CD262
* CD263
* CD264
* CD265
* CD266
* CD267
* CD268
* CD269
* CD271
* CD272
* CD273
* CD274
* CD275
* CD276
* CD278
* CD279
* CD280
* CD281
* CD282
* CD283
* CD284
* CD286
* CD288
* CD289
* CD290
* CD292
* CDw293
* CD294
* CD295
* CD297
* CD298
* CD299

301–350|

* CD300A
* CD301
* CD302
* CD303
* CD304
* CD305
* CD306
* CD307
* CD309
* CD312
* CD314
* CD315
* CD316
* CD317
* CD318
* CD320
* CD321
* CD322
* CD324
* CD325
* CD326
* CD327
* CD328
* CD329
* CD331
* CD332
* CD333
* CD334
* CD335
* CD336
* CD337
* CD338
* CD339
* CD340
* CD344
* CD349
* CD350

* v
* t
* e

Receptors: growth factor receptors

Type I cytokine receptor|

* Nerve growth factors: Ciliary neurotrophic factor
* Erythropoietin

Receptor protein serine/threonine kinase|

* TGF pathway: TGF-beta
* 1
* 2
* Activin
* 1
* 2
* Bone morphogenetic protein
* 1
* 2

Receptor tyrosine kinase|

* Fibroblast growth factor
* 1
* 2
* 3
* 4

* Nerve growth factors: high affinity Trk
* TrkA
* TrkB
* TrkC

* Hepatocyte growth factor

* Somatomedin
* Insulin-like growth factor 1

* ErbB/Epidermal growth factor

* VEGF
* 1
* 2
* 3

Tumor necrosis factor receptor|

* Nerve growth factors: Low affinity/p75

Ig superfamily|

* Platelet-derived growth factor
* A
* B
* Stem cell factor

Other/ungrouped|

* Somatomedin
* Insulin-like growth factor 2

* v
* t
* e

Cytokine receptors

Chemokine receptor
(GPCRs)|

| CC|

* CCR1 / CCRL1
* CCR2
* CCRL2
* CCR3
* CCR4
* CCR5
* CCR6
* CCR7
* CCR8
* CCR9
* CCR10

|

CXC|

* IL-8
* CXCR1
* CXCR2
* CXCR3
* CXCR4
* CXCR5
* CXCR6
* CXCR7

Other|

* CX3C
* CX3CR1
* XC
* XCR1
* CCBP2
* CMKLR1

TNF receptor|

| 1-10|

* TNFR1 (TNFRSF1A)
* TNFR2 (TNFRSF1B)
* LTBR (TNFRSF3)
* CD134 (TNFRSF4)
* CD40 (TNFRSF5)
* Fas receptor (TNFRSF6)
* DcR3 (TNFRSF6B)
* CD27 (TNFRSF7)
* CD30 (TNFRSF8)
* CD137 (TNFRSF9)

|

11-20|

* DR4 (TNFRSF10A)
* DR5 (TNFRSF10B)
* DcR1 (TNFRSF10C)
* DcR2 (TNFRSF10D)
* RANK (TNFRSF11A)
* Osteoprotegerin (TNFRSF11B)
* TweakR (TNFRSF12A)
* TACI (TNFRSF13B)
* BAFFR (TNFRSF13C)
* HVEM (TNFRSF14)
* NGFR (TNFRSF16)
* BCMA (TNFRSF17)
* GITR (TNFRSF18)
* TAJ/TROY (TNFRSF19)

21-27|

* DR6 (TNFRSF21)
* DR3 (TNFRSF25)
* EDA2R (TNFRSF27)

JAK-STAT|

| Type I|

| γ-chain|

* Interleukin receptors
* IL2R / IL2RA/IL2RB / IL15R
* IL4R / IL13R / IL13RA1 / IL13RA2
* IL7R / IL7RA
* IL9R
* IL21R

|

β-chain|

* Interleukin receptors
* IL3R / IL3RA
* IL5R / IL5RA
* GM-CSF

gp130|

* Interleukin receptors
* IL6RA
* 11/IL11RA
* 27/IL27RA
* OSMR
* LIFR
* CNTFR

IL12RB1|

* Interleukin receptors
* IL12R/IL12RB1/IL12RB2
* IL23R

Other|

* other CSF receptors
* EPO
* G-CSF
* Thrombopoietin

* hormone receptor: GH
* prolactin

Type II|

* Interleukin receptors
* IL10R / IL10RA / IL10RB / IL22R / IL22RA1 / IL22RA2
* IL20R / IL20RA / IL20RB
* IL28R
* Interferon receptors
* -α/β / IFNAR1/IFNAR2
* -γ/IFNGR1 / IFNGR2

Ig superfamily|

*   * IL1
* IL1R1
* IL1R2
* IL18R / IL18R1

IL 17 family|

* IL17
* IL17RA
* IL17RB
* IL17RC
* IL17RD
* IL17RE

Enzyme-linked receptor|

* Tyr
* CSF1R
* KIT
* Ser/Thr: TGF-beta
* TGFBR1
* TGFBR2
* family

* v
* t
* e

Tumor suppressor genes and Oncogenes

Ligand|

| Growth factors|

| ONCO|

* c-Sis/PDGF
* HGF

|

Receptor|

| Wnt signaling pathway|

| TSP|

* CDH1

|

Hedgehog signaling pathway|

| TSP|

* PTCH1

|

TGF beta signaling pathway|

| TSP|

* TGF beta receptor 2

|

Receptor tyrosine kinase|

| ONCO|

* ErbB/c-ErbB
* HER2/neu
* Her 3
* c-Met
* c-Ret

|

JAK-STAT signaling pathway|

| ONCO|

* c-Kit
* Flt3

|

Intracellular signaling P+Ps|

| Wnt signaling pathway|

| ONCO|

* Beta-catenin

|

TSP|

* APC

TGF beta signaling pathway|

| TSP|

* SMAD2
* SMAD4

|

Akt/PKB signaling pathway|

| ONCO|

* c-Akt

|

TSP|

* PTEN

Hippo signaling pathway|

| TSP|

* Neurofibromin 2/Merlin

|

MAPK/ERK pathway|

| ONCO|

* c-Ras
* HRAS
* c-Raf

|

TSP|

* Neurofibromin 1

Other/unknown|

| ONCO|

* c-Src

|

TSP|

* Maspin

Nucleus|

| Cell cycle|

| ONCO|

* CDK4
* Cyclin D
* Cyclin E

|

TSP|

* p53
* pRb
* WT1
* p16/p14arf

DNA repair/Fanconi|

| TSP|

* BRCA1
* BRCA2

|

Ubiquitin ligase|

| ONCO|

* CBL
* MDM2

|

TSP|

* VHL

Transcription factor|

| ONCO|

* AP-1
* c-Fos
* c-Jun
* c-Myc

|

TSP|

* KLF6

Mitochondrion|

| Apoptosis inhibitor|

* SDHB
* SDHD

|

Other/ungrouped|

* c-Bcl-2
* Notch
* Stathmin

* v
* t
* e

Protein kinases: tyrosine kinases (EC 2.7.10)

Receptor tyrosine kinases (EC 2.7.10.1)

| Growth factor receptors|

| EGF receptor family|

* EGFR
* ERBB2
* ERBB3
* ERBB4

|

Insulin receptor family|

* IGF1R
* INSR
* INSRR

PDGF receptor family|

* CSF1R
* FLT3
* KIT
* PDGFR (PDGFRA
* PDGFRB)

FGF receptor family|

* FGFR1
* FGFR2
* FGFR3
* FGFR4

VEGF receptors family|

* VEGFR1
* VEGFR2
* VEGFR3

HGF receptor family|

* MET
* RON

Trk receptor family|

* NTRK1
* NTRK2
* NTRK3

EPH receptor family|

* EPHA1
* EPHA2
* EPHA3
* EPHA4
* EPHA5
* EPHA6
* EPHA7
* EPHA8
* EPHB1
* EPHB2
* EPHB3
* EPHB4
* EPHB5
* EPHB6
* EPHX

LTK receptor family|

* LTK
* ALK

TIE receptor family|

* TIE
* TEK

ROR receptor family|

* ROR1
* ROR2

DDR receptor family|

* DDR1
* DDR2

PTK7 receptor family|

* PTK7

RYK receptor family|

* RYK

MuSK receptor family|

* MUSK

ROS receptor family|

* ROS1

AATYK receptor family|

* AATYK
* AATYK2

AXL receptor family|

* AXL
* MER
* TYRO3

RET receptor family|

* RET

uncategorised|

* STYK1

Non-receptor tyrosine kinases (EC 2.7.10.2)

| ABL family|

* ABL1
* ARG

|

ACK family|

* ACK1
* TNK1

CSK family|

* CSK
* MATK

FAK family|

* FAK
* PYK2

FES family|

* FES
* FER

FRK family|

* FRK
* BRK
* SRMS

JAK family|

* JAK1
* JAK2
* JAK3
* TYK2

SRC-A family|

* SRC
* FGR
* FYN
* YES1

SRC-B family|

* BLK
* HCK
* LCK
* LYN

TEC family|

* TEC
* BMX
* BTK
* ITK
* TXK

SYK family|

* SYK
* ZAP70

* v
* t
* e

Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Diffusion-limited enzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
* EC3 Hydrolases (list)
* EC4 Lyases (list)
* EC5 Isomerases (list)
* EC6 Ligases (list)
* EC7 Translocases (list)

* v
* t
* e

Growth factor receptor modulators

Angiopoietin|

* Agonists: Angiopoietin 1
* Angiopoietin 4

* Antagonists: Angiopoietin 2
* Angiopoietin 3

* Kinase inhibitors: Altiratinib
* CE-245677
* Rebastinib

* Antibodies: Evinacumab (against angiopoietin 3)
* Nesvacumab (against angiopoietin 2)

CNTF|

* Agonists: Axokine
* CNTF
* Dapiclermin

EGF (ErbB)|

| EGF
(ErbB1/HER1)|

* Agonists: Amphiregulin
* Betacellulin
* EGF (urogastrone)
* Epigen
* Epiregulin
* Heparin-binding EGF-like growth factor (HB-EGF)
* Murodermin
* Nepidermin
* Transforming growth factor alpha (TGFα)

* Kinase inhibitors: Afatinib
* Agerafenib
* Brigatinib
* Canertinib
* Dacomitinib
* Erlotinib
* Gefitinib
* Grandinin
* Icotinib
* Lapatinib
* Neratinib
* Osimertinib
* Vandetanib
* WHI-P 154

* Antibodies: Cetuximab
* Depatuxizumab
* Depatuxizumab mafodotin
* Futuximab
* Imgatuzumab
* Matuzumab
* Necitumumab
* Nimotuzumab
* Panitumumab
* Zalutumumab

|

ErbB2/HER2|

* Agonists: Unknown/none

* Antibodies: Ertumaxomab
* Pertuzumab
* Trastuzumab
* Trastuzumab deruxtecan
* Trastuzumab duocarmazine
* Trastuzumab emtansine

* Kinase inhibitors: Afatinib
* Lapatinib
* Mubritinib
* Neratinib
* Tucatinib

ErbB3/HER3|

* Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C))

* Antibodies: Duligotumab
* Patritumab
* Seribantumab

ErbB4/HER4|

* Agonists: Betacellulin
* Epigen
* Heparin-binding EGF-like growth factor (HB-EGF)
* Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))

FGF|

| FGFR1|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20)
* Repifermin
* Selpercatinib
* Trafermin
* Velafermin

|

FGFR2|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22)
* Palifermin
* Repifermin
* Selpercatinib
* Sprifermin
* Trafermin

* Antibodies: Aprutumab
* Aprutumab ixadotin

* Kinase inhibitors: Infigratinib

FGFR3|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 4, 8, 9, 18, 23)
* Selpercatinib
* Sprifermin
* Trafermin

* Antibodies: Burosumab (against FGF23)

FGFR4|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 4, 6, 8, 9, 19)
* Trafermin

Unsorted|

* Agonists: FGF15/19

HGF (c-Met)|

* Agonists: Fosgonimeton
* Hepatocyte growth factor

* Potentiators: Dihexa (PNB-0408)

* Kinase inhibitors: Altiratinib
* AM7
* AMG-458
* Amuvatinib
* BMS-777607
* Cabozantinib
* Capmatinib
* Crizotinib
* Foretinib
* Golvatinib
* INCB28060
* JNJ-38877605
* K252a
* MK-2461
* PF-04217903
* PF-2341066
* PHA-665752
* SU-11274
* Tivantinib
* Volitinib

* Antibodies: Emibetuzumab
* Ficlatuzumab
* Flanvotumab
* Onartuzumab
* Rilotumumab
* Telisotuzumab
* Telisotuzumab vedotin

IGF|

| IGF-1|

* Agonists: des(1-3)IGF-1
* Insulin-like growth factor-1 (somatomedin C)
* IGF-1 LR3
* Insulin-like growth factor-2 (somatomedin A)
* Insulin
* Mecasermin
* Mecasermin rinfabate

* Kinase inhibitors: BMS-754807
* Linsitinib
* NVP-ADW742
* NVP-AEW541
* OSl-906

* Antibodies: AVE-1642
* Cixutumumab
* Dalotuzumab
* Figitumumab
* Ganitumab
* Robatumumab
* R1507
* Teprotumumab
* Xentuzumab (against IGF-1 and IGF-2)

|

IGF-2|

* Agonists: Insulin-like growth factor-2 (somatomedin A)

* Antibodies: Dusigitumab
* Xentuzumab (against IGF-1 and IGF-2)

Others|

* Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7)

* Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1)
* Trofinetide

LNGF (p75NTR)|

* Agonists: BDNF
* BNN-20
* BNN-27
* Cenegermin
* DHEA
* DHEA-S
* NGF
* NT-3
* NT-4

* Antagonists: ALE-0540
* Dexamethasone
* EVT-901 (SAR-127963)
* Testosterone

* Antibodies: Against NGF: ABT-110 (PG110)
* ASP-6294
* Fasinumab
* Frunevetmab
* Fulranumab
* MEDI-578
* Ranevetmab
* Tanezumab

* Aptamers: Against NGF: RBM-004

* Decoy receptors: LEVI-04 (p75NTR-Fc)

PDGF|

* Agonists: Becaplermin
* Platelet-derived growth factor (A, B, C, D)

* Kinase inhibitors: Agerafenib
* Avapritinib
* Axitinib
* Crenolanib
* Imatinib
* Lenvatinib
* Masitinib
* Motesanib
* Nintedanib
* Pazopanib
* Radotinib
* Quizartinib
* Ripretinib
* Sunitinib
* Sorafenib
* Toceranib

* Antibodies: Olaratumab
* Ramucirumab
* Tovetumab

RET (GFL)|

| GFRα1|

* Agonists: Glial cell line-derived neurotrophic factor (GDNF)
* Liatermin

* Kinase inhibitors: Vandetanib

|

GFRα2|

* Agonists: Neurturin (NRTN)

* Kinase inhibitors: Vandetanib

GFRα3|

* Agonists: Artemin (ARTN)

* Kinase inhibitors: Vandetanib

GFRα4|

* Agonists: Persephin (PSPN)

* Kinase inhibitors: Vandetanib

Unsorted|

* Kinase inhibitors: Agerafenib

SCF (c-Kit)|

* Agonists: Ancestim
* Stem cell factor

* Kinase inhibitors: Agerafenib
* Axitinib
* Dasatinib
* Imatinib
* Masitinib
* Nilotinib
* Pazopanib
* Quizartinib
* Sorafenib
* Sunitinib
* Toceranib

TGFβ|

* See here instead.

Trk|

| TrkA|

* Agonists: Amitriptyline
* BNN-20
* BNN-27
* Cenegermin
* DHEA
* DHEA-S
* Gambogic amide
* NGF
* Tavilermide

* Antagonists: ALE-0540
* Dexamethasone
* FX007
* Testosterone

* Negative allosteric modulators: VM-902A

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* Milciclib
* ONO-4474
* ONO-5390556
* PLX-7486
* Rebastinib
* SNA-120 (pegylated K252a))

* Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110)
* ASP-6294
* Fasinumab
* Frunevetmab
* Fulranumab
* MEDI-578
* Ranevetmab
* Tanezumab

* Aptamers: Against NGF: RBM-004

* Decoy receptors: ReN-1820 (TrkAd5)

|

TrkB|

* Agonists: 3,7-DHF
* 3,7,8,2'-THF
* 4'-DMA-7,8-DHF
* 7,3'-DHF
* 7,8-DHF
* 7,8,2'-THF
* 7,8,3'-THF
* Amitriptyline
* BDNF
* BNN-20
* Deoxygedunin
* Deprenyl
* Diosmetin
* DMAQ-B1
* HIOC
* LM22A-4
* N-Acetylserotonin
* NT-3
* NT-4
* Norwogonin (5,7,8-THF)
* R7
* R13
* TDP6

* Antagonists: ANA-12
* Cyclotraxin B
* Gossypetin (3,5,7,8,3',4'-HHF)

* Ligands: DHEA

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* ONO-4474
* ONO-5390556
* PLX-7486

TrkC|

* Agonists: BNN-20
* DHEA
* NT-3

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* ONO-4474
* ONO-5390556
* PLX-7486

VEGF|

* Agonists: Placental growth factor (PGF)
* Ripretinib
* Telbermin
* VEGF (A, B, C, D (FIGF))

* Allosteric modulators: Cyclotraxin B

* Kinase inhibitors: Agerafenib
* Altiratinib
* Axitinib
* Cabozantinib
* Cediranib
* Fruquintinib
* Lapatinib
* Lenvatinib
* Motesanib
* Nintedanib
* Pazopanib
* Pegaptanib
* Rebastinib
* Regorafenib
* Semaxanib
* Sorafenib
* Sunitinib
* Toceranib
* Tivozanib
* Vandetanib
* WHI-P 154

* Antibodies: Alacizumab pegol
* Bevacizumab
* Icrucumab
* Ramucirumab
* Ranibizumab

* Decoy receptors: Aflibercept

Others|

* Additional growth factors: Adrenomedullin
* Colony-stimulating factors (see here instead)
* Connective tissue growth factor (CTGF)
* Ephrins (A1, A2, A3, A4, A5, B1, B2, B3)
* Erythropoietin (see here instead)
* Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
* Glia maturation factor (GMF)
* Hepatoma-derived growth factor (HDGF)
* Interleukins/T-cell growth factors (see here instead)
* Leukemia inhibitory factor (LIF)
* Macrophage-stimulating protein (MSP; HLP, HGFLP)
* Midkine (NEGF2)
* Migration-stimulating factor (MSF; PRG4)
* Oncomodulin
* Pituitary adenylate cyclase-activating peptide (PACAP)
* Pleiotrophin
* Renalase
* Thrombopoietin (see here instead)
* Wnt signaling proteins

* Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)

* v
* t
* e

Cytokine receptor modulators

Chemokine|

* See here instead.

CSF|

| Erythropoietin|

* Agonists: ARA-290
* Asialo erythropoietin
* Carbamylated erythropoietin
* CNTO-530
* Darbepoetin alfa
* Epoetin alfa
* Epoetin beta
* Epoetin delta
* Epoetin epsilon
* Epoetin gamma
* Epoetin kappa
* Epoetin omega
* Epoetin theta
* Epoetin zeta
* Erythropoietin (EPO)
* Erythropoietin-Fc
* Methoxy polyethylene glycol-epoetin beta (CERA/Mircera)
* Peginesatide
* Pegol sihematide (EPO-018B)

|

G-CSF (CSF3)|

* Agonists: Filgrastim
* Granulocyte colony-stimulating factor
* Lenograstim
* Leridistim
* Lipegfilgrastim
* Nartograstim
* Pegfilgrastim
* Pegnartograstim

GM-CSF (CSF2)|

* Agonists: Ecogramostim
* Granulocyte macrophage colony-stimulating factor
* Milodistim
* Molgramostim
* Regramostim
* Sargramostim

* Antibodies: Mavrilimumab
* Namilumab
* Otilimab

M-CSF (CSF1)|

* Agonists: Cilmostim
* Interleukin-34
* Lanimostim
* Macrophage colony-stimulating factor
* Mirimostim

* Kinase inhibitors: Agerafenib

SCF (c-Kit)|

* See here instead.

Thrombopoietin|

* Agonists: Eltrombopag
* Pegacaristim
* Promegapoietin
* Romiplostim
* Thrombopoietin (THPO, MGDF)

Interferon|

| IFNAR (α/β, I)|

* Agonists: Albinterferon
* Interferon alpha (interferon alfa, IFN-α)
* Interferon alfa (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21)
* Interferon alfa 2a
* Interferon alfa 2b
* Interferon alfa n1
* Interferon alfacon-1
* Interferon alpha-n3
* Interferon beta (IFN-β) (IFNB1, IFNB3)
* Interferon beta 1a
* Interferon beta 1b
* Interferon kappa (IFN-ε/κ/τ/ζ, IFNK)
* Interferon omega (IFN-ω, IFNW1)
* Peginterferon alfa-2a
* Peginterferon alfa-2b

* Antibodies: Anifrolumab
* Faralimomab
* MEDI-545
* Rontalizumab
* Sifalimumab

* Decoy receptors: Bifarcept

|

IFNGR (γ, II)|

* Agonists: Interferon gamma (IFN-γ)
* Interferon gamma 1b

* Antibodies: Emapalumab
* Fontolizumab

IFNLR (λ, III)|

* See IL-28R (IFNLR) here instead.

Interleukin|

* See here instead.

TGFβ|

* See here instead.

TNF|

* See here instead.

Others|

| JAK
(inhibitors)|

| JAK1|

* Abrocitinib
* Baricitinib
* Deuruxolitinib
* Filgotinib
* Momelotinib
* Oclacitinib
* Peficitinib
* Ruxolitinib
* Tofacitinib (tasocitinib)
* Upadacitinib

|

JAK2|

* Atiprimod
* AZD-1480
* Baricitinib
* CHZ868
* Cucurbitacin I (elatericin B, JSI-124)
* CYT387
* Deuruxolitinib
* Lestaurtinib
* NSC-7908
* NSC-33994
* Pacritinib
* Peficitinib
* Ruxolitinib
* SD-1008
* Tofacitinib (tasocitinib)

JAK3|

* Cercosporamide
* Decernotinib (VX-509)
* Peficitinib
* Ritlecitinib
* TCS-21311
* Tofacitinib (tasocitinib)
* WHI-P 154
* ZM-39923
* ZM-449829

TYK2|

* Deucravacitinib

Others|

* Additional cytokines: Cardiotrophin 1 (CT-1)
* FMS-like tyrosine kinase 3 ligand (FLT3L)
* Leukemia/leukocyte inhibitory factor (LIF)
* Oncostatin M (OSM)
* Thymic stromal lymphopoietin (TSLP)

* Additional cytokine receptor modulators: Emfilermin
* Lestaurtinib
* Midostaurin
* Quizartinib
* Sorafenib
* Sunitinib

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