CD117

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V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
PBB Protein KIT image.jpg
PDB rendering based on 1pkg.
Available structures: 1pkg, 1t45, 1t46
Identifiers
Symbol(s) KIT; C-Kit; CD117; SCFR
External IDs OMIM: 164920 MGI96677 Homologene187
Orthologs
Human Mouse
Entrez 3815 16590
Ensembl na ENSMUSG00000005672
Uniprot na Q3ULJ6
Refseq NM_000222 (mRNA)
NP_000213 (protein)
NM_021099 (mRNA)
NP_066922 (protein)
Location na Chr 5: 75.86 - 75.94 Mb
Pubmed search [1] [2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

Overview

CD117, also called KIT or C-kit receptor, is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. This receptor binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer.[1]


This gene encodes the human homolog of the proto-oncogene c-kit. C-kit was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. This protein is a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene.[2]


Cell Surface Marker

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. CD117 is an important cell surface marker used to identify certain types of hematopoietic (blood) progenitors in the bone marrow. Specifically hematopoietic stem cells (HSC), multipotent progenitors (MPP), and common myeloid progenitors (CMP) express high levels of CD117. Common lymphoid progenitors (CLP) expresses low surface levels of CD117.

CD117 also identifies the earliest thymocyte progenitors in the thymus. Specifically early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit.

Additionally mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express CD117.

Ligand

CD117 is the receptor for the cytokine stem cell factor (SCF), also known as "steel factor" or "c-kit ligand". SCF exists in two forms, cell surface bound SCF and soluble (or free) SCF.

Function

CD117 is a receptor tyrosine kinase type III. When this receptor binds to SCF it forms a dimer which activates signaling through second messengers. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation.

Mobilization

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 CD117 has been implicated in mobilization. Currently, G-CSF is the main drug used for mobilization. G-CSF indirectly activates CD117. Direct CD117 agonists are currently being developed as mobilization agents.

Role in cancer

CD117 is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer.[3] Seminomas, a subtype of testicular germ cell tumors, frequently have activating mutations in exon 17 of CD117. In addition, the gene encoding CD117 is frequently overexpressed and amplified in this tumour type, most commonly occurring as a single gene amplicon.[4] Mutations of CD117 have also been implicated in leukemia, a cancer of hematopoietic progenitors, and gastrointestinal stromal tumors (GISTs). The efficacy of imatinib, a CD117 inhibitor, is determined by the mutation status of CD117.

See also

References

  1. Edling CE, Hallberg B (2007). "c-Kit--a hematopoietic cell essential receptor tyrosine kinase". Int. J. Biochem. Cell Biol. 39 (11): 1995–8. doi:10.1016/j.biocel.2006.12.005. PMID 17350321.
  2. Entrez Gene: KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog.
  3. Jean-Loup Huret. KIT. Atlas of Genetics and Cytogenetics in Oncology and Haematology. Retrieved on 2008-03-01.
  4. McIntyre A, Summersgill B, Grygalewicz B, Gillis AJ, Stoop J, van Gurp RJ, Dennis N, Fisher C, Huddart R, Cooper C, Clark J, Oosterhuis JW, Looijenga LH, Shipley J (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 Res. 65 (18): 8085–9. doi:10.1158/0008-5472.CAN-05-0471. PMID 16166280.

Further reading

  • Linnekin D (2000). "Early signaling pathways activated by c-Kit in hematopoietic cells.". Int. J. Biochem. Cell Biol. 31 (10): 1053-74. PMID 10582339.
  • Canonico B, Felici C, Papa S (2001). "CD117.". J. Biol. Regul. Homeost. Agents 15 (1): 90-4. PMID 11388751.
  • Gupta R, Bain BJ, Knight CL (2002). "Cytogenetic and molecular genetic abnormalities in systemic mastocytosis.". Acta Haematol. 107 (2): 123-8. PMID 11919394.
  • Valent P, Ghannadan M, Hauswirth AW, et al. (2003). "Signal transduction-associated and cell activation-linked antigens expressed in human mast cells.". Int. J. Hematol. 75 (4): 357-62. PMID 12041664.
  • Sandberg AA, Bridge JA (2002). "Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. gastrointestinal stromal tumors.". Cancer Genet. Cytogenet. 135 (1): 1-22. PMID 12072198.
  • Kitamura Y, Hirotab S (2005). "Kit as a human oncogenic tyrosine kinase.". Cell. Mol. Life Sci. 61 (23): 2924-31. doi:10.1007/s00018-004-4273-y. PMID 15583854.
  • Larizza L, Magnani I, Beghini A (2005). "The Kasumi-1 cell line: a t(8;21)-kit mutant model for acute myeloid leukemia.". Leuk. Lymphoma 46 (2): 247-55. doi:10.1080/10428190400007565. PMID 15621809.
  • Miettinen M, Lasota J (2006). "KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation.". Appl. Immunohistochem. Mol. Morphol. 13 (3): 205-20. PMID 16082245.
  • Lasota J, Miettinen M (2007). "KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs).". Semin Diagn Pathol 23 (2): 91-102. PMID 17193822.
  • Patnaik MM, Tefferi A, Pardanani A (2007). "Kit: molecule of interest for the diagnosis and treatment of mastocytosis and other neoplastic disorders.". Current cancer drug targets 7 (5): 492-503. PMID 17691909.
  • Giebel LB, Strunk KM, Holmes SA, Spritz RA (1992). "Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene.". Oncogene 7 (11): 2207-17. PMID 1279499.
  • Spritz RA, Droetto S, Fukushima Y (1992). "Deletion of the KIT and PDGFRA genes in a patient with piebaldism.". Am. J. Med. Genet. 44 (4): 492-5. doi:10.1002/ajmg.1320440422. PMID 1279971.
  • Spritz RA, Giebel LB, Holmes SA (1992). "Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism.". Am. J. Hum. Genet. 50 (2): 261-9. PMID 1370874.
  • Duronio V, Welham MJ, Abraham S, et al. (1992). "p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein.". Proc. Natl. Acad. Sci. U.S.A. 89 (5): 1587-91. PMID 1371879.
  • André C, Martin E, Cornu F, et al. (1992). "Genomic organization of the human c-kit gene: evolution of the receptor tyrosine kinase subclass III.". Oncogene 7 (4): 685-91. PMID 1373482.
  • Lev S, Yarden Y, Givol D (1992). "A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses.". J. Biol. Chem. 267 (15): 10866-73. PMID 1375232.
  • Fleischman RA (1992). "Human piebald trait resulting from a dominant negative mutant allele of the c-kit membrane receptor gene.". J. Clin. Invest. 89 (6): 1713-7. PMID 1376329.
  • Vandenbark GR, deCastro CM, Taylor H, et al. (1992). "Cloning and structural analysis of the human c-kit gene.". Oncogene 7 (7): 1259-66. PMID 1377810.
  • Alai M, Mui AL, Cutler RL, et al. (1992). "Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells.". J. Biol. Chem. 267 (25): 18021-5. PMID 1381360.
  • Ashman LK, Cambareri AC, To LB, et al. (1991). "Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow.". Blood 78 (1): 30-7. PMID 1712644.

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