Diverse Signaling Pathways Activated by Growth Factor Receptors Induce Broadly Overlapping, Rather Than Independent, Sets

Cell, Vol. 97, 727?741, June, 1999. Published: 1999.05.31

Douglas Fambrough, Kimberly McClure, Andrius Kazlauskas, and Eric S. Lander.

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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 receptor (PDGFR) signaling. Mutant receptors lacking binding sites for activation of the PLC, 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 and fibroblast growth factor receptor 1; each induces essentially identical IEGs in fibroblasts

Keywords: growth factor receptors receptor tyrosine kinase signaling pathways,gene expression

Supplemental Data

Description Link/Filename
general http://www-genome.wi.mit.edu/RTK/index.html
summary http://www-genome.wi.mit.edu/RTK/Summary.html
data http://www-genome.wi.mit.edu/RTK/Dataset.html
tables http://www-genome.wi.mit.edu/RTK/Tables.html