Comprehensive Dissection of PDGF-PDGFR Signaling Pathways in PDGFR Genetically Defined Cells
Open accessAbstract
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.
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Upregulation of SOS1, SOS2 and RTKs (ERBB2 and ERBB3), as well as CXCL16 and PDGFA, was observed as early as 4 h post-last dose of combination treatment.
“On the molecular level, upregulation of SOS1, SOS2 and RTKs (for example ERBB2 and ERBB3), as well as CXCL16 and PDGFA, both associated with activation of the MAPK and/or PI3K signaling32,33, was observed as early as 4 h post-last dose of combination treatment (Fig. 5b).”
From Co-targeting SOS1 enhances the antitumor effects of KRASG12C inhibitors by addressing intrinsic and acquired resistance (2024) · cites this paper as [33]
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- Authors
- Wu, E., Palmer, N., Tian, Z., Moseman, A. P., Galdzicki, M., Wang, X., Berger, B., Zhang, H., & Kohane, I. S.
- Affiliations
- Boston Children's Hospital (US)
- MIT Computer Science and Artificial Intelligence Laboratory (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Kohane, Isaac S.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-11-24
- Volume
- 3
- Issue
- 11
- Pages
- e3794
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2582946
- OpenAlex
- W2156268500
- Cited by
- 118
- References
- 42
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 17 · 2018: 6 · 2017: 2 · 2016: 7 · 2015: 7 · 2014: 8 · 2013: 9 · 2012: 10
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- U.S. National Library of Medicine (2 TA5 LM 07092-11, T15LM007092)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- PDGF signaling, PDGFRA, PDGFRβ, PDGF-BB, receptor heterodimerization, receptor redundancy, mouse embryonic fibroblasts, cell proliferation, cell differentiation, gene expression profiling
- MeSH terms
- Becaplermin, Animals, Cells, Cultured, Fibroblasts, Gene Expression Regulation, Platelet-Derived Growth Factor, Signal Transduction, Receptors, Platelet-Derived Growth Factor, Proto-Oncogene Proteins c-sis, Receptor, Platelet-Derived Growth Factor alpha, Receptor, Platelet-Derived Growth Factor beta, Gene Expression Profiling, Cell Proliferation, Mice, Gene Knockout Techniques
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