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

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 PDGFRalph...

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Bibliographic Details
Published in:PloS one 2008-11, Vol.3 (11), p.e3794-e3794
Main Authors: Wu, Erxi, Palmer, Nathan, Tian, Ze, Moseman, Annie P, Galdzicki, Michal, Wang, Xuetao, Berger, Bonnie, Zhang, Hongbing, Kohane, Isaac S
Format: Article
Language:English
Subjects:
Acids
Analysis
Angiogenesis
Animals
Artificial intelligence
Biology
Cancer
Cell adhesion & migration
Cell Biology
Cell Biology/Cell Signaling
Cell Biology/Gene Expression
Cell growth
Cell Proliferation
Cells, Cultured
Children & youth
Computer science
Consortia
Dissection
Embryo fibroblasts
Embryos
Fibroblasts
Gene expression
Gene Expression Profiling
Gene Expression Regulation - genetics
Gene Knockout Techniques
Genes
Genomes
Genomics
Health sciences
Informatics
Kinases
Laboratories
Medical schools
Mice
Null cells
Ontology
Pathogenesis
Pharmacology
Platelet-derived growth factor
Platelet-Derived Growth Factor - pharmacology
Platelet-derived growth factor BB
Proteins
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
Receptors, Platelet-Derived Growth Factor - genetics
Receptors, Platelet-Derived Growth Factor - physiology
Redundancy
Signal Transduction
Smooth muscle
Studies
Surgery
Tumors
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0003794