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Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes
Author(s): Fambrough D, McClure K, Kazlauskas A, Lander ES
Source: CELL    Volume: 97    Issue: 6    Pages: 727-741    Published: JUN 11 1999  
Times Cited: 321     References: 59     
Abstract: We 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 (PDGFR beta) signaling. Mutant receptors lacking binding sites for activation of the PLC gamma, 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 PDGFR beta and fibroblast growth factor receptor 1; each induces essentially identical IEGs in fibroblasts.
Document Type: Article
Language: English
Reprint Address: Lander, ES (reprint author), Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA
Addresses:
1. Schepens Eye Res Inst, Boston, MA 02114 USA
2. MIT, Dept Biol, Cambridge, MA 02139 USA
Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA
Subject Category: Biochemistry & Molecular Biology; Cell Biology
IDS Number: 206NQ
ISSN: 0092-8674
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