CD117
Encyclopedia
Mast/stem cell growth factor receptor (SCFR) also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117 is a protein
that in humans is encoded by the KIT gene
. Multiple transcript variants encoding different isoforms have been found for this gene.
CD117 was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.
(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
. To be specific, 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
. To be specific, early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit. It is also a marker for mouse prostate
stem cell
s. In addition, mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express CD117.
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
... CD117 is a receptor tyrosine kinase
type III, which binds to stem cell factor
(a substance that causes certain types of cells to grow), also known as "steel factor" or "c-kit ligand". When this receptor binds to 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. Signalling through CD117 plays a role in cell survival, proliferation, and differentiation.
s, testicular seminoma, mast cell disease, melanoma, acute myeloid leukemia, while inactivating mutations are associated with the genetic defect piebaldism
.
CD117 is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer. 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 tumor type, most commonly occurring as a single gene amplicon. Mutations of CD117 have also been implicated in leukemia
, a cancer of hematopoietic progenitors, melanoma, mast cell disease, and gastrointestinal stromal tumor
s (GISTs). The efficacy of imatinib
(trade name Gleevec), a CD117 inhibitor, is determined by the mutation status of CD117.
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 leukemia), the receptor is not inhibited by imatinib
. In those cases other inhibitors such as dasatinib
and nilotinib
can be used.
to help distinguish particular types of tumour in histological
tissue sections. It is used primarily in the diagnosis of GISTs, which are positive for CD117, 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, CD117 staining is typically cytoplasm
ic, with stronger accentuation along the cell membrane
s. CD117 antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing seminomas from embryonal carcinoma
s.
with:
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the KIT gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Multiple transcript variants encoding different isoforms have been found for this gene.
CD117 was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.
Cell Surface Marker
Cluster of differentiationCluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
(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
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. To be specific, 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
Thymocyte
Thymocytes are hematopoietic progenitor cells present in the thymus. Thymopoiesis is the process in the thymus by which thymocytes differentiate into mature T lymphocytes. The primary function of thymocytes is the generation of T lymphocytes . The thymus provides an inductive environment, which...
progenitors in the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
. To be specific, early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit. It is also a marker for mouse prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s. In addition, mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express CD117.
Function
CD117 is a cytokine receptorCytokine receptor
Cytokine receptors are receptors that bind cytokines.In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been...
expressed on the surface of hematopoietic stem cells as well as other cell types. Altered
Altered
Altered is a science fiction horror film released straight-to-DVD in 2006. Altered was directed by Eduardo Sánchez, co-director of the box office hit The Blair Witch Project.-Synopsis:...
forms of this receptor may be associated with some types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
... CD117 is a receptor tyrosine kinase
Receptor tyrosine kinase
Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
type III, which binds to stem cell factor
Stem cell factor
Stem Cell Factor is a cytokine that binds to the c-Kit receptor . SCF can exist both as a transmembrane protein and a soluble protein...
(a substance that causes certain types of cells to grow), also known as "steel factor" or "c-kit ligand". When this receptor binds to SCF it forms a dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. Signalling 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. At the current time, 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
Activating mutations in this gene are associated with gastrointestinal stromal tumorGastrointestinal stromal tumor
A gastrointestinal stromal tumor is one of the most common mesenchymal tumors of the gastrointestinal tract...
s, testicular seminoma, mast cell disease, melanoma, acute myeloid leukemia, while inactivating mutations are associated with the genetic defect piebaldism
Piebaldism
Piebaldism is a rare autosomal dominant disorder of melanocyte development. Common characteristics include a congenital white forelock, scattered normal pigmented and hypopigmented macules and a triangular shaped depigmented patch on the forehead....
.
CD117 is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer. 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 tumor type, most commonly occurring as a single gene amplicon. Mutations of CD117 have also been implicated in leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
, a cancer of hematopoietic progenitors, melanoma, mast cell disease, and gastrointestinal stromal tumor
Gastrointestinal stromal tumor
A gastrointestinal stromal tumor is one of the most common mesenchymal tumors of the gastrointestinal tract...
s (GISTs). The efficacy of imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...
(trade name Gleevec), a CD117 inhibitor, is determined by the mutation status of CD117.
When the mutation has occurred in exon 11 (as is the case many times in GISTs), the tumors are responsive to imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...
. However, if the mutation occurs in exon 17 (as is often the case in seminomas and leukemia), the receptor is not inhibited by imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...
. In those cases other inhibitors such as dasatinib
Dasatinib
Dasatinib, previously known as BMS-354825, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is an oral multi- BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia after imatinib treatment...
and nilotinib
Nilotinib
Nilotinib , in the form of the hydrochloride monohydrate salt, is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia.-Uses:...
can be used.
Diagnostic relevance
Antibodies to CD117 are widely used in immunohistochemistryImmunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
to help distinguish particular types of tumour in histological
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
tissue sections. It is used primarily in the diagnosis of GISTs, which are positive for CD117, but negative for markers such as desmin
Desmin
Desmin is a protein that in humans is encoded by the DES gene.Desmin is a type III intermediate filament found near the Z line in sarcomeres. It was first described in 1976, first purified in 1977, the gene was cloned in 1989, and the first knock-out mouse was created in 1996. Desmin is only...
and S-100, which are positive in smooth muscle
Leiomyosarcoma
Leiomyosarcoma , aka LMS, is a malignant cancer of smooth muscle....
and neural tumors, which have a similar appearance. In GISTs, CD117 staining is typically cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic, with stronger accentuation along the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s. CD117 antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing seminomas from embryonal carcinoma
Embryonal carcinoma
Embryonal carcinoma is a relatively uncommon type of germ cell tumour that occurs in the ovaries and testes.-Ovarian embryonal carcinoma:In the ovary, embryonal carcinoma is quite rare, amounting to approximately three percent of ovarian germ cell tumours. The median age at diagnosis is 15 years...
s.
Interactions
CD117 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- APS,
- BCRBCR geneThe BCR gene is one of the two genes in the bcr-abl complex, which is associated with the Philadelphia chromosome.-Pathology:...
, - CD63CD63CD63 antigen is a protein that in humans is encoded by the CD63 gene.CD63 is a good marker for flow cytometric quantification of in vitro activated basophils for diagnosis of IgE-mediated allergy. The test is commonly designated as basophil activation test -Interactions:CD63 has been shown to...
, - CD81CD81CD81 molecule, also known as CD81 , is a protein which in humans is encoded by the CD81 gene...
, - CD9CD9CD9 antigen is a protein that in humans is encoded by the CD9 gene.-Interactions:CD9 has been shown to interact with TSPAN4, PTGFRN, CD81, CD117, CD46, CD29 and CD49c.-Further reading:...
, - CRKCRKCRK can refer to:* Chris Reeve Knives, an American knife manufacturer* Český Radioklub, an amateur radio organization in the Czech Republic* Diosdado Macapagal International Airport* CRK...
, - CRKLCRKLCrk-like protein is a protein that in humans is encoded by the CRKL gene.CrkL together with Crk participates in the Reelin signaling cascade downstream of DAB1.-Interactions:...
, - DOK1DOK1Docking protein 1 is a protein that in humans is encoded by the DOK1 gene.-Interactions:DOK1 has been shown to interact with RET proto-oncogene, SH2D1A, LYN, RAS p21 protein activator 1, INPP5D, CD117, SHC1, Abl gene and TEC.-Further reading:...
, - FESFESFES or Fes may refer to:* Fes or Fez, a city in Morocco* FES , a human gene that encodes the feline sarcoma oncogene enzyme* FES , a fictional singer from Chaos;Head anime series and alias of Yui Sakakibara for her songs from Chaos;Head and Steins;Gate anime series* Flywheel energy storage, an...
, - GRB10GRB10Growth factor receptor-bound protein 10 also known as insulin receptor-binding protein Grb-IR is a protein that in humans is encoded by the GRB10 gene.- Function :...
, - Grb2Grb2Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....
, - KITLGStem cell factorStem Cell Factor is a cytokine that binds to the c-Kit receptor . SCF can exist both as a transmembrane protein and a soluble protein...
, - LNKLNKLNK or lnk is a three letter acronym that has several meanings:*IATA airport code for Lincoln Airport in Lincoln, Nebraska*Amtrak station code for Lincoln, Nebraska *LNK , a television station in Lithuania...
, - LYNLYNTyrosine-protein kinase Lyn is a protein that in humans is encoded in humans by the LYN gene.Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells, in neural tissues liver, and adipose tissue. In various hematopoietic cells, Lyn has emerged...
, - MATKMegakaryocyte-associated tyrosine kinaseMegakaryocyte-associated tyrosine-protein kinase is an enzyme that in humans is encoded by the MATK gene.-Interactions:Megakaryocyte-associated tyrosine kinase has been shown to interact with CD117 and TrkA.-Further reading:...
, - MPDZMPDZMultiple PDZ domain protein is a protein that in humans is encoded by the MPDZ gene.-Interactions:MPDZ has been shown to interact with CD117, PLEKHA1 and 5-HT2C receptor.-Further reading:...
, - PIK3R1PIK3R1Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.-Interactions:PIK3R1 has been shown to interact with EPH receptor A2, KHDRBS1, Lymphocyte cytosolic protein 2, Janus kinase 2, GAB2, CD117, BCAR1, CD28, SHB, EZR, PIK3CD, GAB1, HRAS,...
, - PTPN11PTPN11Tyrosine-protein phosphatase non-receptor type 11 also known as protein-tyrosine phosphatase 1D or protein-tyrosine phosphatase 2C is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase Shp2.PTPN11 is a member of the protein tyrosine phosphatase ...
, - PTPN6PTPN6Tyrosine-protein phosphatase non-receptor type 6 is an enzyme that in humans is encoded by the PTPN6 gene.Also known as Src homology region 2 domain-containing phosphatase-1 .-Interactions:...
, - STAT1STAT1STAT1 is a member of the Signal Transducers and Activators of Transcription family of transcription factors. STAT1 is involved in upregulating genes due to a signal by either type I, type II or type III interferons...
, - SOCS1Suppressor of cytokine signaling 1Suppressor of cytokine signaling 1 is a protein that in humans is encoded by the SOCS1 gene. SOCS1 orthologs have been identified in several mammals for which complete genome data are available.-Interactions:...
, - SOCS6,
- SRCSRC-Education:* Sulaiman Al Rajhi Colleges, a private, non-profit university comprising three graduate colleges, located in Al Bukayriyah, Saudi Arabia* Sid Richardson College, one of nine residential colleges on the Rice University campus in Houston, Texas, USA...
, and - TECTEC (gene)Tyrosine-protein kinase Tec is an enzyme that in humans is encoded by the TEC gene.-Interactions:TEC has been shown to interact with GNA12, Janus kinase 2, CD117, Suppressor of cytokine signaling 1, ARHGEF12 and DOK1.-Further reading:...
.
External links
- C-kit receptor entry in the public domain NCI Dictionary of Cancer Terms