Platelet-derived growth factor receptor family (PDGFR) (PDGFR)

The Platelet-derived growth factor receptor (PDGFR) family comprises two main receptor tyrosine kinases, PDGFRA (alpha) and PDGFRB (beta), which are essential mediators of mesenchymal cell signaling (UniProt P16234, P09619). Upon binding of their respective PDGF ligands, these receptors undergo dimerization and autophosphorylation, activating intracellular cascades such as the PI3K/Akt, Ras/MAPK, and PLC-gamma pathways to regulate cell proliferation, migration, and survival (PubMed: 29158374). While critical for normal physiological processes like embryonic development and wound healing, aberrant PDGFR signaling is a hallmark of several diseases. Mutations or gene rearrangements in PDGFRA and PDGFRB are primary drivers in gastrointestinal stromal tumors (GIST), certain myeloproliferative neoplasms, and glioblastomas (PubMed: 15184875). Furthermore, overactivation of these receptors contributes to the progression of fibrotic disorders and cardiovascular diseases like atherosclerosis (PubMed: 24607168). Pharmacological targeting of the PDGFR family has been highly successful, utilizing small-molecule tyrosine kinase inhibitors like imatinib and sunitinib, as well as monoclonal antibodies like olaratumab, to inhibit downstream signaling and tumor growth (DrugBank DB00619).

Other names

PDGFRsCD140Platelet-derived growth factor receptorsPDGF receptor alpha and beta

Drugs targeting the PDGFR family primarily function through two mechanisms: small-molecule tyrosine kinase inhibitors (TKIs) compete with ATP for the binding site within the intracellular catalytic domain, preventing autophosphorylation and downstream signaling; alternatively, monoclonal antibodies bind to the extracellular domain of the receptor, sterically hindering ligand binding and receptor dimerization (PubMed: 29158374, DrugBank DB00619).