Scientific Publications

Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes

Publication TypeJournal Article
AuthorsFambrough, D., McClure K., Kazlauskas A., and Lander E. S.
AbstractWe sought to explore the relationship between receptor tyrosine kinase (RTK) activated signaling pathways and the transcriptional induction of immediate early genes (IEGs). Using global expression monitoring, we identified 66 fibroblast IEGs induced by platelet-derived growth factor beta receptor (PDGFRbeta) signaling. Mutant receptors lacking binding sites for activation of the PLCgamma, PI3K, SHP2, and RasGAP pathways still retain partial ability to induce 64 of these IEGs. Removal of the Grb2-binding site further broadly reduces induction. These results suggest that the diverse pathways exert broadly overlapping effects on IEG induction. Interestingly, a mutant receptor that restores the RasGAP-binding site promotes induction of an independent group of genes, normally induced by interferons. Finally, we compare the PDGFRbeta and fibroblast growth factor receptor 1; each induces essentially identical IEGs in fibroblasts.
Year of Publication1999
JournalCell
Volume97
Issue6
Pages727 - 41
Date Published (YYYY/MM/DD)1999/06/11/
ISBN Number0092-8674
Keywords3T3 Cells, Animals, Cancer, Cell Line, Fibroblast Growth F, Fibroblasts, Gene Expression Regulation, Genes, Humans, Immediate-Early, Interferon Type II, Mice, Mutagenesis, Overlapping, Phenylalanine, Receptor, Receptor Protein-Tyrosine Kinases, Transformed