PDGFRA

Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) is a protein that in humans is encoded by the PDGFRA gene. PDGFRA is a cell surface receptor that belongs to the tyrosine kinase family of proteins. It plays a crucial role in various cellular processes, including cell proliferation, cell differentiation, and wound healing, by mediating the effects of its ligands, primarily the platelet-derived growth factors (PDGFs).

Structure

PDGFRA is composed of an extracellular domain, a single transmembrane domain, and an intracellular domain that contains the tyrosine kinase activity. The extracellular region is responsible for binding to PDGFs, while the intracellular region, upon activation, initiates a cascade of phosphorylation events leading to the activation of downstream signaling pathways.

Function

The primary function of PDGFRA is to mediate the biological effects of PDGFs, which are key factors in angiogenesis, tissue regeneration, and the development of several organs. Upon binding to its ligands, PDGFRA dimerizes (either with itself or with its closely related family member, PDGFRB), leading to the activation of its kinase activity. This activation triggers a series of downstream signaling pathways, including the PI3K/AKT/mTOR pathway, the RAS/RAF/MEK/ERK pathway, and the PLCγ pathway, which are involved in controlling cell growth, survival, and migration.

Clinical Significance

Mutations and overexpression of PDGFRA have been implicated in various forms of cancer, including gastrointestinal stromal tumors (GISTs), gliomas, and dermatofibrosarcoma protuberans. In GISTs, mutations in PDGFRA are associated with a subset of these tumors, and the presence of such mutations can influence the choice of treatment, as some mutations confer sensitivity to specific tyrosine kinase inhibitors (TKIs) like imatinib.

Therapeutic Target

Given its role in cancer, PDGFRA has been targeted for therapeutic intervention. Tyrosine kinase inhibitors, such as imatinib, sunitinib, and others, have been developed to inhibit the kinase activity of PDGFRA, thereby blocking the proliferative signals in tumors that depend on this pathway for growth and survival. The effectiveness of these inhibitors varies depending on the type of mutation present in the PDGFRA gene.

See Also

• Platelet-derived growth factor
• Tyrosine kinase inhibitor
• Gastrointestinal stromal tumor