Platelet-derived growth factor receptor

PDGFR-beta 3MJG

Platelet-derived growth factor receptor (PDGFR) is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor (PDGF) family. PDGFR plays a crucial role in various cellular processes, including growth, proliferation, and differentiation.

Structure[edit | edit source]

PDGFR exists in two forms, PDGFR-α and PDGFR-β, which are encoded by the PDGFRA and PDGFRB genes, respectively. Both receptors are composed of an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. The extracellular domain contains five immunoglobulin-like loops that are responsible for binding to PDGF ligands.

Function[edit | edit source]

PDGFR is activated upon binding to its ligands, PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, and PDGF-DD. Ligand binding induces receptor dimerization and autophosphorylation of specific tyrosine residues within the intracellular domain. This autophosphorylation creates docking sites for downstream signaling molecules, initiating various signaling pathways such as the PI3K/AKT pathway, the Ras/MAPK pathway, and the PLCγ pathway. These pathways regulate cellular processes including survival, proliferation, migration, and differentiation.

Role in Disease[edit | edit source]

Aberrant PDGFR signaling has been implicated in several diseases, particularly in various types of cancer and fibrosis. Mutations in PDGFRA and PDGFRB genes can lead to constitutive activation of the receptor, contributing to oncogenesis. For example, PDGFRA mutations are commonly found in gastrointestinal stromal tumors (GISTs). Overexpression of PDGFR has also been observed in diseases such as idiopathic pulmonary fibrosis and systemic sclerosis.

Therapeutic Target[edit | edit source]

Given its role in disease, PDGFR is a target for therapeutic intervention. Several tyrosine kinase inhibitors (TKIs) have been developed to inhibit PDGFR signaling. Imatinib, for instance, is a TKI that targets PDGFR and is used in the treatment of GISTs and other malignancies. Other inhibitors, such as sunitinib and pazopanib, also target PDGFR and are used in various cancer therapies.