Class III receptor tyrosine kinase (Class III RTK)

Class III receptor tyrosine kinases (RTKs) are a distinct subfamily of cell-surface receptors characterized by an extracellular region containing five immunoglobulin-like domains and an intracellular region with a split tyrosine kinase domain [1, 2]. This family includes five key members: Platelet-Derived Growth Factor Receptors (PDGFRα and PDGFRβ), KIT (Stem Cell Factor Receptor), FLT3 (Fms-like tyrosine kinase 3), and CSF1R (Colony-Stimulating Factor 1 Receptor) [2]. These receptors are essential for regulating hematopoiesis, angiogenesis, and the development of mesenchymal cells by activating downstream pathways like PI3K/AKT, MAPK/ERK, and STAT [1, 3]. Mutations or overexpression of Class III RTKs are frequently implicated in the pathogenesis of various cancers, such as acute myeloid leukemia (AML), gastrointestinal stromal tumors (GIST), and systemic mastocytosis [2, 4]. Because of their central role in oncogenesis, they are primary targets for small-molecule tyrosine kinase inhibitors (TKIs) [5]. Drugs such as imatinib, sunitinib, and midostaurin work by binding to the ATP-binding pocket of the kinase domain, effectively blocking signal transduction [5, 6]. Despite their clinical success, the emergence of secondary resistance mutations and systemic toxicities like myelosuppression remain significant challenges in therapy [3, 6].

Other names

Type III receptor tyrosine kinasePDGFR familySplit-kinase domain receptor familyPlatelet-derived growth factor receptor family

Small-molecule inhibition of the intracellular tyrosine kinase domain by competing with ATP binding, thereby preventing downstream signaling cascades.