• What is PDGFRA?
  • Clinical Trials


The platelet derived growth factor receptor alpha (PDGFRA) belongs to a family of receptor tyrosine kinases (RTKs) that include PDGFRA and PDGFRB. The binding of ligands, such as platelet derived growth factor (PDGF), induces a conformational change that facilitates receptor homo- or heterodimer formation, thereby resulting in activation of PDGFRA tyrosine kinase activity. Activated PDGFRA then phosphorylates its substrates, resulting in activation of multiple downstream pathways within the cell, including the PI3K-AKT-mTOR pathway, which is involved in cell survival, and the RAS-RAF-MEK-ERK pathway, which is involved in cell proliferation (Figure 1).

Mutant PDGFRA has been implicated in the pathogenesis of a number of cancers. For example, mutations are found in gastrointestinal stromal tumors (GIST; Corless et al. 2005Heinrich et al. 2003), and fusions are found in hypereosinophilic syndrome (Cools et al. 2003). In dermatofibrosarcoma protuberans, PDGFRA is activated by a PDGFB fusion protein; as a result, imatinib, as a PDGFRA inhibitor, has shown activity and is approved for clinical use (Labropoulos and Razis 2007; Simon et al. 1997).



Figure 1.
Schematic of PDGFRA signaling pathways. The binding of the ligand, platelet-derived growth factor (PDGF), to the PDGFRA receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Robert G. Maki, M.D., Ph.D., FACP, Vicki Keedy, M.D., M.S.C.I.

Suggested Citation: Maki, R., V. Keedy. 2016. PDGFRA. My Cancer Genome https://www.padiracinnovation.org/content/disease/gist/pdgfra/?tab=0 (Updated May 26).

Last Updated: May 26, 2016


PDGFRA is mutated in ~5% of GIST, most frequently in gastric GIST. Specifically, PDGFRA mutations are found mostly in exons 18 (tyrosine kinase 2 (TK2) domain; ~5%), 12 (juxtamembrane domain; 1%) and 14 (tyrosine kinase 1 (TK1) domain; <1%). Mutations except for D842V in exon 18 are sensitive to imatinib (Corless et al. 2005).


Contributors: Robert G. Maki, M.D., Ph.D., FACP, Vicki Keedy, M.D., M.S.C.I.

Suggested Citation: Maki, R., V. Keedy. 2015. PDGFRA in GIST. My Cancer Genome https://www.padiracinnovation.org/content/disease/gist/pdgfra/ (Updated June 18).

Last Updated: June 18, 2015

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