The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Evolutionary Divergence of Platelet-Derived Growth Factor Alpha Receptor Signaling Mechanisms
Open accessAbstract
Receptor tyrosine kinases (RTKs) direct diverse cellular and developmental responses by stimulating a relatively small number of overlapping signaling pathways. Specificity may be determined by RTK expression patterns or by differential activation of individual signaling pathways. To address this issue we generated knock-in mice in which the extracellular domain of the mouse platelet-derived growth factor alpha receptor (PDGFalphaR) is fused to the cytosolic domain of Drosophila Torso (alpha(Tor)) or the mouse fibroblast growth factor receptor 1 (alpha(FR)). alpha(Tor) homozygous embryos exhibit significant rescue of neural crest and angiogenesis defects normally found in PDGFalphaR-null embryos yet fail to rescue skeletal or extraembryonic defects. This phenotype was associated with the ability of alpha(Tor) to stimulate the mitogen-activated protein (MAP) kinase pathway to near wild-type levels but failure to completely activate other pathways, such as phosphatidylinositol (PI) 3-kinase. The alpha(FR) chimeric receptor fails to rescue any aspect of the PDGFalphaR-null phenotype. Instead, alpha(FR) expression leads to a gain-of-function phenotype highlighted by ectopic bone development. The alpha(FR) phenotype was associated with a failure to limit MAP kinase signaling and to engage significant PI3-kinase response. These results suggest that precise regulation of divergent downstream signaling pathways is critical for specification of RTK function.
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Metadata
- Authors
- Hamilton, T. G., Klinghoffer, R. A., Corrin, P. D., & Soriano, P.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-06
- Volume
- 23
- Issue
- 11
- Pages
- 4013-4025
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2166323322
- Cited by
- 434
- References
- 37
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- green
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- Hamilton, T. G., Klinghoffer, R. A., Corrin, P. D., & Soriano, P. (2003). Evolutionary Divergence of Platelet-Derived Growth Factor Alpha Receptor Signaling Mechanisms. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.23.11.4013-4025.2003
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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