PDGFreceptorer

PDGFreceptorer (platelet-derived growth factor receptors) are a family of receptor tyrosine kinases that mediate responses to platelet-derived growth factors. They play a central role in the regulation of mesenchymal cell proliferation, migration and differentiation during development and tissue repair, as well as in pathological states such as fibrosis and cancer.

There are two main receptor subtypes in humans: PDGFR-α and PDGFR-β, encoded by the genes PDGFRA and PDGFRB. Each receptor has an extracellular ligand-binding region composed of immunoglobulin-like domains, a single-pass transmembrane segment, and an intracellular tyrosine kinase domain. PDGFRs are activated upon binding to PDGF ligands, which include PDGF-A, PDGF-B, PDGF-C and PDGF-D. The receptors form homo- or heterodimers (αα, αβ, ββ) that undergo trans-autophosphorylation on cytoplasmic tyrosine residues, creating docking sites for signaling proteins.

Activated PDGFR signaling engages multiple pathways, notably the PI3K-Akt, Ras-MAPK and PLCγ cascades, along with Src family kinases. These pathways regulate cell cycle progression, survival, cytoskeletal rearrangement and migration, contributing to developmental processes such as vasculature formation and tissue remodeling, as well as to wound healing and maintenance of pericytes and smooth muscle cells.

Alterations in PDGFR signaling are implicated in various diseases. Overexpression or constitutive activation can support tumor growth and stromal support in cancers, while paracrine signaling contributes to fibrotic diseases. A characteristic example is dermatofibrosarcoma protuberans, where PDGF signaling drives tumorigenesis. Therapeutically, PDGFR activity can be targeted by tyrosine kinase inhibitors (for example imatinib and related agents), which have shown clinical benefit in selected tumors and fibrotic conditions.