PDGFRα, PDGFRβ, FGFR1–4, and c-Kit

PDGFRα, PDGFRβ, FGFR1–4, and c-Kit are structurally related type III and type IV receptor tyrosine kinases involved in signal transduction regulating cell growth, survival, migration, and differentiation in numerous tissues. They are key drivers of developmental processes and adult tissue maintenance and are abnormally activated in various malignancies, fibrotic conditions, and other proliferative diseases. Their extracellular domains bind dimeric growth factor ligands (PDGFs for PDGFRα/β, FGFs for FGFR1–4, stem cell factor for c-Kit), resulting in receptor dimerization, autophosphorylation, and stimulation of downstream signaling pathways such as MAPK and PI3K/Akt. Therapeutically, these receptors are inhibited by numerous kinase inhibitors that disrupt cell proliferation and survival in cancers and other diseases with aberrant receptor signaling. Their importance as biomarkers, and the complexities of their signaling and drug response, make them prominent subjects in targeted drug development and precision medicine.

Other names

CD140aCD140bCD117KIT

Kinase inhibition: block ATP-binding site of the intracellular kinase domain to inhibit downstream signaling. Antagonism/blockade: prevent receptor dimerization and activation. Downregulation/Degradation: promote receptor internalization and turnover