Signaling by PDGFRA extracellular domain mutants

Mutations in the extracellular domain of receptor tyrosine kinases like PDGRFA have the potential to interfere with glycosylation, which is required for proper trafficking to the cell surface. Versions of PDGFRA bearing mutations in the extracellular domain have been identified in some cancers, and while some of these are inactive, some have also been shown to signal constitutively from the endoplasmic reticulum. PDGFRA Y288C carries a mutation in the extracellular domain of the receptor that prevents the normal trafficking of the protein to the plasma membrane. PDGFRA Y288C is trapped in the endoplasmic reticulum membrane, from where it is able to signal constitutively in the absence of ligand. Similarly, a version of PDGFRA bearing an in-frame deletion of exons 8 and 9 has been identified in glioblastoma. The resulting protein is constitutively active in the absence of ligand despite the low fraction of protein expressed at the cell surface.

Summary from Reactome (R-HSA-9673770), read 2026-09-23.