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 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.
Wu
Erxi
E
Informatics Program, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America.
Palmer
Nathan
N
Tian
Ze
Z
Moseman
Annie P
AP
Galdzicki
Michal
M
Wang
Xuetao
X
Berger
Bonnie
B
Zhang
Hongbing
H
Kohane
Isaac S
IS
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
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