Platelet-derived growth factor receptor alpha (PDGFRα) (PDGFRα)

Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase that plays a fundamental role in embryonic development, cell proliferation, and survival (UniProt P16234). It is activated upon binding with its ligands, PDGF-A, -B, and -C, which leads to receptor dimerization and the phosphorylation of specific tyrosine residues in its cytoplasmic domain (NCBI Gene ID: 5156). This process initiates several intracellular signaling cascades, including the PI3K/AKT, Ras/MAPK, and PLCγ pathways, which are essential for the growth and migration of mesenchymal cells. In pathological contexts, PDGFRα is frequently dysregulated through gene mutations, amplifications, or translocations, contributing significantly to the pathogenesis of gastrointestinal stromal tumors (GIST), glioblastomas, and certain myeloid neoplasms (PubMed: 15340161). Anlotinib is a multi-targeted tyrosine kinase inhibitor that potently inhibits PDGFRα along with VEGFR and FGFR, thereby blocking both tumor cell proliferation and tumor-associated angiogenesis (PubMed: 29156761). Therapeutic targeting of PDGFRα is a standard approach in treating cancers where the receptor is constitutively active, though specific resistance mutations like D842V present ongoing clinical challenges.

Other names

PDGFRACD140APDGFR2Alpha-type platelet-derived growth factor receptorPlatelet-derived growth factor receptor 2Rhe-PDGFRA

Competitive inhibition of the adenosine triphosphate (ATP) binding site within the intracellular tyrosine kinase domain, which prevents autophosphorylation and blocks downstream signaling pathways.