PDGFRA Human

Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) is a cell surface tyrosine kinase receptor that plays a crucial role in various cellular processes. It is encoded by the PDGFRA gene and is part of the receptor tyrosine kinase (RTK) family, specifically the class III subfamily . PDGFRA is involved in the regulation of cell growth, development, and differentiation, making it a significant focus of research in developmental biology and oncology.

PDGFRA is a type I transmembrane glycoprotein that consists of an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular tyrosine kinase domain . The receptor is activated upon binding to its ligands, which are members of the platelet-derived growth factor (PDGF) family. These ligands include PDGF-AA, PDGF-BB, and PDGF-CC . Upon ligand binding, PDGFRA dimerizes, leading to autophosphorylation and activation of its kinase activity. This activation triggers downstream signaling pathways that regulate various cellular functions such as proliferation, migration, and survival .

PDGFRA is integrally involved in embryonic development, angiogenesis, and organogenesis . It induces fibroblast proliferation and migration, which are essential processes in wound healing and tissue repair . PDGFRA is expressed in various cell types, including epithelial cells, muscle cells, osteosarcoma cells, and neuronal progenitor cells . Its role in organ development and wound healing highlights its importance in maintaining tissue homeostasis.

Mutations and aberrant activation of PDGFRA have been implicated in several diseases, including idiopathic hypereosinophilic syndrome, gastrointestinal stromal tumors (GISTs), and other cancers . In GISTs, PDGFRA mutations are often mutually exclusive with KIT mutations and are considered a hallmark of the disease . These mutations can lead to constitutive activation of the receptor, driving uncontrolled cell proliferation and tumor growth. Additionally, PDGFRA gene fusions are associated with eosinophilia and are classified as a distinct disorder by the World Health Organization .

Given its role in various cancers, PDGFRA is a target for therapeutic interventions. Tyrosine kinase inhibitors (TKIs) such as imatinib have been developed to inhibit the activity of PDGFRA and are used in the treatment of GISTs . However, resistance to TKIs can occur due to secondary mutations in the PDGFRA gene. Research is ongoing to develop new therapeutic strategies to overcome resistance and improve patient outcomes.

Recombinant human PDGFRA is produced using recombinant DNA technology, which involves the insertion of the PDGFRA gene into a suitable expression system, such as bacterial or mammalian cells. This allows for the large-scale production of the receptor for research and therapeutic purposes. Recombinant PDGFRA is used in various studies to understand its structure, function, and role in disease, as well as to develop and test new therapeutic agents.