The emerging complexity of PDGFRs: activation, internalization and signal attenuation

Biochem Soc Trans. 2020 Jun 30;48(3):1167-1176. doi: 10.1042/BST20200004.


The platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases allows cells to communicate with the environment to regulate diverse cellular activities. Here, we highlight recent data investigating the structural makeup of individual PDGFRs upon activation, revealing the importance of the whole receptor in the propagation of extracellular ligand binding and dimerization. Furthermore, we review ongoing research demonstrating the significance of receptor internalization and signal attenuation in the regulation of PDGFR activity. Interactions with internalization machinery, signaling from endosomes, receptor degradation and receptor recycling are physiological means by which cells fine-tune PDGFR responses to growth factor stimulation. In this review, we discuss the biophysical, structural, in silico and biochemical data that have provided evidence for these mechanisms. We further highlight the commonalities and differences between PDGFRα and PDGFRβ signaling, revealing critical gaps in knowledge. In total, this review provides a conclusive summary on the state of the PDGFR field and underscores the need for novel techniques to fully elucidate the mechanisms of PDGFR activation, internalization and signal attenuation.

Keywords: PDGFR; RTK; signaling.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Computer Simulation
  • Endosomes / metabolism
  • Humans
  • Ligands*
  • Phosphorylation
  • Protein Multimerization
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Signal Transduction*


  • Ligands
  • PDGFRB protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta