Reference - Detail
| RRC ID | 68425 |
|---|---|
| Author | Nakakuki T, Birtwistle MR, Saeki Y, Yumoto N, Ide K, Nagashima T, Brusch L, Ogunnaike BA, Okada-Hatakeyama M, Kholodenko BN. |
| Title | Ligand-specific c-Fos expression emerges from the spatiotemporal control of ErbB network dynamics. |
| Journal | Cell |
| Abstract |
Activation of ErbB receptors by epidermal growth factor (EGF) or heregulin (HRG) determines distinct cell-fate decisions, although signals propagate through shared pathways. Using mathematical modeling and experimental approaches, we unravel how HRG and EGF generate distinct, all-or-none responses of the phosphorylated transcription factor c-Fos. In the cytosol, EGF induces transient and HRG induces sustained ERK activation. In the nucleus, however, ERK activity and c-fos mRNA expression are transient for both ligands. Knockdown of dual-specificity phosphatases extends HRG-stimulated nuclear ERK activation, but not c-fos mRNA expression, implying the existence of a HRG-induced repressor of c-fos transcription. Further experiments confirmed that this repressor is mainly induced by HRG, but not EGF, and requires new protein synthesis. We show how a spatially distributed, signaling-transcription cascade robustly discriminates between transient and sustained ERK activities at the c-Fos system level. The proposed control mechanisms are general and operate in different cell types, stimulated by various ligands. |
| Volume | 141(5) |
| Pages | 884-96 |
| Published | 2010-5-28 |
| DOI | 10.1016/j.cell.2010.03.054 |
| PII | S0092-8674(10)00373-9 |
| PMID | 20493519 |
| PMC | PMC2888034 |
| MeSH | Cell Line, Tumor Dual-Specificity Phosphatases / metabolism ErbB Receptors / metabolism Extracellular Signal-Regulated MAP Kinases / metabolism Humans Models, Biological* Neuregulin-1 / metabolism Protein Stability Proto-Oncogene Proteins c-fos / genetics* Proto-Oncogene Proteins c-fos / metabolism Transcription, Genetic |
| IF | 38.637 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | F1000Research |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | PC-12(RCB0009) |