Cells communicate and interact through specialized proteins on their surfaces. These cell surface markers act like identification tags, allowing cells to recognize each other and respond to external cues. Understanding these markers helps unravel processes governing health and disease. Among these, CD117 is a significant protein with a multifaceted role.
Understanding CD117
CD117, also known as c-Kit or KIT, is a cell surface receptor. It is a member of the receptor tyrosine kinase (RTK) family, proteins that transmit signals from outside the cell to its interior. Structurally, CD117 is a transmembrane protein, meaning it spans the cell membrane to receive and relay signals.
The extracellular domain of CD117 contains five immunoglobulin-like domains, important for binding signaling molecules. The intracellular portion features a tyrosine kinase domain, split by a hydrophilic insert sequence of approximately 80 amino acids. When a signal molecule binds to the extracellular part, it triggers a change in the receptor’s shape, activating the tyrosine kinase domain and initiating cellular events.
Cells That Express CD117
CD117 is found on the surface of several distinct cell types throughout the body, reflecting its diverse functions. It is expressed on hematopoietic stem cells, which are precursors to all blood cells. It supports their ability to self-renew and differentiate into various blood cell lineages.
Beyond blood-forming cells, CD117 is also found on mast cells, immune cells involved in allergic reactions and inflammatory responses. Additionally, germ cells, involved in reproduction, and interstitial cells of Cajal (ICCs) in the gastrointestinal tract, also express CD117. ICCs are known as the pacemaker cells of the gut, regulating digestive tract motility.
How CD117 Functions in the Body
The physiological function of CD117 is initiated when it binds to its specific ligand, Stem Cell Factor (SCF), also known as c-kit ligand. Its binding to CD117 causes two CD117 receptors to dimerize on the cell surface. This dimerization activates the intrinsic tyrosine kinase activity within the intracellular domain of CD117.
Upon activation, the tyrosine kinase domain phosphorylates specific tyrosine residues within the receptor and on other proteins. This phosphorylation acts as a molecular switch, activating various downstream signaling pathways. The activation of these pathways promotes cellular activities, including cell growth, proliferation, differentiation, survival, and migration, crucial for normal physiological processes.
CD117 and Its Role in Health and Disease
CD117’s presence and function are important in both healthy biological processes and disease development. As a diagnostic marker, CD117 expression is important for identifying Gastrointestinal Stromal Tumors (GISTs). Approximately 85% of GISTs exhibit mutations in the KIT gene, leading to CD117 overexpression or abnormal activation.
CD117 is also expressed in some cases of Acute Myeloid Leukemia (AML), where its presence can be associated with drug tolerance and a less favorable prognosis. In mastocytosis, a disorder characterized by an excessive accumulation of mast cells, CD117 mutations are frequently observed. The altered or overactive CD117 signaling pathways contribute to uncontrolled cell growth and survival in these conditions.
Given its role in disease, CD117 has become a target for therapeutic interventions, particularly in cancer treatment. Drugs like imatinib, a tyrosine kinase inhibitor, specifically block the activity of CD117. Imatinib is approved for treating certain CD117-positive GISTs, including certain unresectable or metastatic cases, and as an adjuvant therapy. This targeted approach aims to inhibit the aberrant signaling driven by mutated or overexpressed CD117, thereby controlling disease progression.