PDGFR dimer-specific activation, trafficking and downstream signaling dynamics

J Cell Sci. 2022 Sep 1;135(17):jcs259686. doi: 10.1242/jcs.259686. Epub 2022 Sep 7.


Signaling through the platelet-derived growth factor receptors (PDGFRs) plays a critical role in multiple cellular processes during development. The two PDGFRs, PDGFRα and PDGFRβ, dimerize to form homodimers and/or heterodimers. Here, we overcome previous limitations in studying PDGFR dimer-specific dynamics by generating cell lines stably expressing C-terminal fusions of each PDGFR with bimolecular fluorescence complementation (BiFC) fragments corresponding to the N-terminal or C-terminal regions of the Venus fluorescent protein. We find that PDGFRβ receptors homodimerize more quickly than PDGFRα receptors in response to PDGF ligand, with increased levels of autophosphorylation. Furthermore, we demonstrate that PDGFRα homodimers are trafficked and degraded more quickly, whereas PDGFRβ homodimers are more likely to be recycled back to the cell membrane. We show that PDGFRβ homodimer activation results in a greater amplitude of phospho-ERK1/2 and phospho-AKT signaling, as well as increased proliferation and migration. Finally, we demonstrate that inhibition of clathrin-mediated endocytosis leads to changes in cellular trafficking and downstream signaling, particularly for PDGFRα homodimers. Collectively, our findings provide significant insight into how biological specificity is introduced to generate unique responses downstream of PDGFR engagement. This article has an associated First Person interview with the first author of the paper.

Keywords: Migration; PDGFRα; PDGFRβ; Proliferation; Signaling; Trafficking.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Humans
  • Phosphorylation
  • Protein Multimerization
  • Receptor, Platelet-Derived Growth Factor alpha* / genetics
  • Receptor, Platelet-Derived Growth Factor alpha* / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Signal Transduction*


  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta