title: Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR genetically defined cells.
abstract: 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.
authors.affiliation: Informatics Program, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
authors.forename: Nathan
authors.initials: N
authors.lastname: Palmer
authors.forename: Ze
authors.initials: Z
authors.lastname: Tian
authors.forename: Annie P
authors.initials: AP
authors.lastname: Moseman
authors.forename: Michal
authors.initials: M
authors.lastname: Galdzicki
authors.forename: Xuetao
authors.initials: X
authors.lastname: Wang
authors.forename: Bonnie
authors.initials: B
authors.lastname: Berger
authors.forename: Hongbing
authors.initials: H
authors.lastname: Zhang
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
mesh_terms: D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation; D002478:Cells, Cultured; D005347:Fibroblasts; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D055786:Gene Knockout Techniques; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000502:physiology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor