KIT

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

KIT, also known as CD117, is a type of receptor tyrosine kinase that is encoded by the KIT gene in humans. This protein plays a crucial role in cell signaling, which is essential for various cellular processes including cell growth, differentiation, and survival. KIT is particularly important in the development and function of certain cell types, such as hematopoietic stem cells, melanocytes, and germ cells.

Structure

KIT is a transmembrane protein that consists of an extracellular domain, a transmembrane domain, and an intracellular tyrosine kinase domain. The extracellular domain is responsible for binding to its ligand, stem cell factor (SCF), which triggers dimerization and activation of the receptor.

Function

The primary function of KIT is to act as a receptor for stem cell factor (SCF), also known as steel factor or mast cell growth factor. Upon binding to SCF, KIT undergoes dimerization and autophosphorylation, activating its kinase activity. This activation initiates a cascade of downstream signaling pathways, including the PI3K/AKT pathway, RAS/RAF/MEK/ERK pathway, and JAK/STAT pathway, which are involved in cell proliferation, survival, and differentiation.

Clinical Significance

Mutations in the KIT gene can lead to various diseases and conditions. Gain-of-function mutations are associated with several types of cancers, including gastrointestinal stromal tumors (GISTs), mastocytosis, and certain types of leukemia. These mutations result in constitutive activation of the KIT receptor, leading to uncontrolled cell proliferation.

Loss-of-function mutations in KIT can result in piebaldism, a condition characterized by patches of unpigmented skin and hair due to the absence of melanocytes.

Therapeutic Target

KIT is a target for several therapeutic agents, particularly in the treatment of cancers such as GISTs. Imatinib, a tyrosine kinase inhibitor, is commonly used to treat GISTs by inhibiting the activity of mutant KIT proteins. Other inhibitors, such as sunitinib and regorafenib, are also used in cases where imatinib resistance develops.

Research

Ongoing research is focused on understanding the detailed mechanisms of KIT signaling and its role in various diseases. There is also significant interest in developing new therapeutic agents that can more effectively target KIT and overcome resistance to current treatments.

Also see

• Receptor tyrosine kinase
• Stem cell factor
• Gastrointestinal stromal tumor
• Imatinib
• Piebaldism