KIT

GeneName

KIT

Summary

KIT, also known as c kit or CD117, is a 110kDa transmembrane receptor protein that functions as a receptor tyrosine kinase. It is primarily expressed in hematopoietic cells, mast cells, and germ cells, and is localised to the plasma membrane and cytoplasm. KIT plays a pivotal role in various biological processes, including cell migration, differentiation of B cells and mast cells, and regulation of hematopoietic stem cell activity. It binds to stem cell factor (SCF), which activates downstream signalling pathways essential for cellular functions. Additionally, KIT is involved in the organization of the actin cytoskeleton and has roles in embryonic development and sensory perception.

Importance

KIT is relevant to: - Cancer research, particularly in gastrointestinal stromal tumours (GISTs) where mutations in KIT are common - Understanding mast cell biology and its implications in allergic responses and mastocytosis - Stem cell research due to its role in stem cell maintenance and differentiation - Developmental biology, especially in processes like melanocyte and germ cell development - Mechanisms of cell migration and proliferation, which are crucial in various physiological and pathological contexts

Top Products

For researchers investigating KIT, we highly recommend the top-selling recombinant antibody, Anti-c-Kit antibody [YR145] (ab32363). This antibody has been validated in knockout models, ensuring reliable performance in your experiments. It is particularly effective for immunohistochemistry (IHC) and western blotting (WB), making it a versatile choice for various applications. With 73 citations, this antibody is well-regarded in the research community, reflecting its trustworthiness and efficacy in detecting KIT. The APC/Cy7® Anti-c-Kit antibody (ab194808) is a reliable option for researchers looking to study the c-Kit protein in their experiments.

Abcam Product Citation Summary

The data indicates that the KIT antibody (ab32363) has been employed in various applications, including immunohistochemistry and Western blotting, across different species and contexts. Notably, it has been used in studies related to neural crest cell migration, vascular progenitor cells in Marfan syndrome, and c-kit activation in cardiac progenitor cells, highlighting its relevance in cardiovascular and developmental research.

Abcam Product Citation Table

Function

Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.

Involvement in disease

Piebald trait

PBT

Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.

None

The disease is caused by variants affecting the gene represented in this entry.

Gastrointestinal stromal tumor

GIST

Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery.

None

The gene represented in this entry is involved in disease pathogenesis.

Testicular germ cell tumor

TGCT

A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.

None

The gene represented in this entry may be involved in disease pathogenesis.

Leukemia, acute myelogenous

AML

A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.

None

The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase.

Mastocytosis, cutaneous

MASTC

A form of mastocytosis, a heterogeneous group of disorders associated with abnormal proliferation and accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. MASTC is an autosomal dominant form characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed Darier sign.

None

The disease is caused by variants affecting the gene represented in this entry.

Mastocytosis, systemic

MASTSYS

A severe form of mastocytosis characterized by abnormal proliferation and accumulation of mast cells in several organs, resulting in a systemic disease that may affect bone, gastrointestinal tract, lymphatics, spleen, and liver. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. It can also lead to mast cell leukemia, which carries a high risk of mortality.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation.

Autophosphorylated on tyrosine residues. KITLG/SCF binding enhances autophosphorylation. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF (in vitro). Kinase activity is down-regulated by phosphorylation on serine residues by protein kinase C family members. Phosphorylation at Tyr-568 is required for interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of the SRC tyrosine-protein kinase family. Phosphorylation at Tyr-570 is required for interaction with PTPN6/SHP-1. Phosphorylation at Tyr-703, Tyr-823 and Tyr-936 is important for interaction with GRB2. Phosphorylation at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at Tyr-823 and Tyr-936 is important for interaction with GRB7.

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Tissue Specificity

Isoform 3

In testis, detected in spermatogonia in the basal layer and in interstitial Leydig cells but not in Sertoli cells or spermatocytes inside the seminiferous tubules (at protein level) (PubMed:20601678). Expression is maintained in ejaculated spermatozoa (at protein level) (PubMed:20601678).

Cellular localization

• Isoform 1
• Cell membrane
• Single-pass type I membrane protein
• Isoform 2
• Cell membrane
• Single-pass type I membrane protein
• Isoform 3
• Cytoplasm
• Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head.

Alternative names

CD117, SCFR, KIT, Mast/stem cell growth factor receptor Kit, Piebald trait protein, Proto-oncogene c-Kit, Tyrosine-protein kinase Kit, p145 c-kit, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog, PBT

Database links

swissprot:P10721 entrezGene:3815 omim:164920

Other research areas

• Immunology & Infectious Disease