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- Title
Comprehensive Dissection of PDGF-PDGFR Signaling Pathways in PDGFR Genetically Defined Cells.
- Authors
Erxi Wu; Palmer, Nathan; Ze Tian; Moseman, Annie P.; Galdzicki, Michal; Xuetao Wang; Berger, Bonnie; Hongbing Zhang; Kohane, Isaac S.
- Abstract
Despite the growing understanding of PDGF signaling, studies of PDGF function have encountered two major obstacles: the functional redundancy of PDGFRα and PDGFRβ in vitro and their distinct roles in vivo. Here we used wild-type mouse embryonic fibroblasts (MEF), MEF null for either PDGFRα, β, 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 PDGFRα, PDGFRβ and PDGFRα/β while each receptor is also responsible for regulating unique signaling pathways. Furthermore, some signaling is solely modulated through heterodimeric PDGFRα/β.
- Subjects
FIBROBLASTS; CELL differentiation; GENE expression; CELL proliferation; CELL migration; PROTEIN-tyrosine kinases; PLATELET-derived growth factor
- Publication
PLoS ONE, 2008, Vol 3, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0003794