C-KIT

C-KIT
Structure of the C-KIT protein
Identifiers
Symbol	?
NCBI gene	3815
HGNC	6342
OMIM	164920
RefSeq	NM_000222
UniProt	P10721
Search for Structures Swiss-model Domains InterPro

C-KIT, also known as CD117, is a type of receptor tyrosine kinase that is encoded by the KIT gene in humans. It plays a crucial role in cell signaling, influencing cell survival, proliferation, and differentiation. C-KIT is particularly important in the development of certain cell types, including hematopoietic stem cells, melanocytes, and germ cells.

Structure

C-KIT is a transmembrane protein that consists of an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain is responsible for binding to its ligand, stem cell factor (SCF), while the intracellular domain has kinase activity that initiates downstream signaling pathways.

Function

C-KIT functions as a receptor for stem cell factor (SCF), also known as steel factor or mast cell growth factor. Upon binding to SCF, C-KIT undergoes dimerization and autophosphorylation, activating its kinase activity. This activation triggers several downstream signaling pathways, including the PI3K/AKT pathway, RAS/MAPK pathway, and JAK/STAT pathway, which are involved in cell survival, proliferation, and differentiation.

Role in Development

C-KIT is essential for the development of various cell types. It is critical for the survival and proliferation of hematopoietic stem cells, which give rise to all blood cell types. It also plays a role in the development of melanocytes, the cells responsible for pigment production in the skin, and germ cells, which are precursors to sperm and eggs.

Clinical Significance

Mutations in the KIT gene can lead to various diseases. Gain-of-function mutations are associated with gastrointestinal stromal tumors (GISTs), mastocytosis, and certain types of leukemia. These mutations result in constitutive activation of the C-KIT receptor, leading to uncontrolled cell proliferation. C-KIT is also a target for cancer therapies, with drugs such as imatinib being used to inhibit its activity in tumors.

Research and Therapeutic Implications

Research on C-KIT has led to the development of targeted therapies for cancers that involve C-KIT mutations. Understanding the role of C-KIT in normal and pathological conditions continues to be an important area of study, with implications for regenerative medicine and cancer treatment.

Also see

• Receptor tyrosine kinase
• Stem cell factor
• Gastrointestinal stromal tumor
• Hematopoietic stem cell
• Imatinib