PDGFRA Gene

The PDGFRA gene (localization on chromosome 4q12), is a protein-coding gene. PDGFRA is the acronym for "platelet-derived growth factor receptor, alpha" . The gene product is platelet-derived growth factor receptor-alpha (PDGFRA/CD140A), which belongs to the family of receptor tyrosine kinases (RTKs).

Physiological functions of PDGFRA - gene and PDGFRA receptor protein:

PDGFRA receptor protein functions as a cell surface receptor for its ligands: PDGFA, PDGFB and PDGFC. The binding of these ligands leads to the activation of different signaling cascades. The response depends on the type of ligand bound and is modulated by the formation of heterodimers between PDGFRA and PDGFRB.

The cognate ligands are:

• homodimeric PDGFA
• homodimeric PDGFB
• homodimeric PDGFC

• heterodimers of PDGFA and PDGFB
  

PDGFRA plays an essential role in regulating embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, it promotes or inhibits cell proliferation and cell migration. The PDGFRA receptor protein plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeletal development and cranial closure during embryonic development.

PDGFRA is required for normal development of the mucosa lining the gastrointestinal tract, recruitment of mesenchymal cells, and normal development of the intestinal villi.

The PDGFRA gene plays a role in wound healing by affecting cell migration and chemotaxis .Mediates the activation of HRAS and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, and STAT5A and/or STAT5B. Receptor signaling is downregulated by protein phosphatases that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor.

Furthermore, the PDGFRA gene plays a role in platelet activation, secretion of agonists from platelet granules, and thrombin-induced platelet aggregation.

Diseases associated with PDGFRA include:

• Gastrointestinal stromal tum ors (GIST; 5% of GIST have mutations in the PDGFRA gene).
• GIST-plus syndrome (MIM:175510): autosomal dominant inherited disorder characterized by multiple mesenchymal tumors of the gastrointestinal tract, including gastrointestinal stromal tumors, inflammatory fibroid polyps, and fibroid tumors. Other features include a coarse face and skin, broad hands and feet, and premature tooth loss.
• Idiopathic hypereosinophilia syndrome.

Related metabolic pathways include the ErbB pathway.

1. Duan Y et al. (2020) Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal Tumors: Rationale and Progress. Cancers (Basel) 12: 2972.
2. Qu SQ et al. (2013) [FIP1L1-PDGFRA positive chronic eosinophilic leukemia with imatinib-resistant T674I mutant of PDGFRA gene: a case report and literature review]. Zhonghua Xue Ye Xue Za Zhi 34:159-161.