Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR genetically defined cells

PLoS One. 2008;3(11):e3794. doi: 10.1371/journal.pone.0003794. Epub 2008 Nov 24.


Despite the growing understanding of pdgf signaling, studies of pdgf function have encountered two major obstacles: the functional redundancy of PDGFRalpha and PDGFRbeta in vitro and their distinct roles in vivo. Here we used wild-type mouse embryonic fibroblasts (MEF), MEF null for either PDGFRalpha, beta, or both to dissect PDGF-PDGFR signaling pathways. These four PDGFR genetically defined cells provided us a platform to study the relative contributions of the pathways triggered by the two PDGF receptors. They were treated with PDGF-BB and analyzed for differential gene expression, in vitro proliferation and differential response to pharmacological effects. No genes were differentially expressed in the double null cells, suggesting minimal receptor-independent signaling. Protean differentiation and proliferation pathways are commonly regulated by PDGFRalpha, PDGFRbeta and PDGFRalpha/beta while each receptor is also responsible for regulating unique signaling pathways. Furthermore, some signaling is solely modulated through heterodimeric PDGFRalpha/beta.

Publication types

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

MeSH terms

  • Animals
  • Becaplermin
  • Cell Proliferation
  • Cells, Cultured
  • Fibroblasts
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics*
  • Gene Knockout Techniques
  • Mice
  • Platelet-Derived Growth Factor / pharmacology
  • Proto-Oncogene Proteins c-sis
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / physiology
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / physiology
  • Receptors, Platelet-Derived Growth Factor / genetics*
  • Receptors, Platelet-Derived Growth Factor / physiology*
  • Signal Transduction*


  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Becaplermin
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptors, Platelet-Derived Growth Factor