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

D Fambrough, K McClure, A Kazlauskas, ES Lander - Cell, 1999 - cell.com
D Fambrough, K McClure, A Kazlauskas, ES Lander
Cell, 1999cell.com
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 β receptor (PDGFRβ) signaling. Mutant receptors lacking binding sites for
activation of the PLCγ, 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 …
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 β receptor (PDGFRβ) signaling. Mutant receptors lacking binding sites for activation of the PLCγ, 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 PDGFRβ and fibroblast growth factor receptor 1; each induces essentially identical IEGs in fibroblasts.
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