Receptor Level Mechanisms Are Required for Epidermal Growth Factor (EGF)-stimulated Extracellular Signal-regulated Kinase (ERK) Activity Pulses.
| Autor: | Sparta B; From the Departments of Molecular and Cellular Biology and., Pargett M; From the Departments of Molecular and Cellular Biology and., Minguet M; From the Departments of Molecular and Cellular Biology and., Distor K; From the Departments of Molecular and Cellular Biology and., Bell G; Microbiology and Molecular Genetics, University of California, Davis, California 95616., Albeck JG; From the Departments of Molecular and Cellular Biology and jgalbeck@ucdavis.edu. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of biological chemistry [J Biol Chem] 2015 Oct 09; Vol. 290 (41), pp. 24784-92. Date of Electronic Publication: 2015 Aug 24. |
| DOI: | 10.1074/jbc.M115.662247 |
| Abstrakt: | In both physiological and cell culture systems, EGF-stimulated ERK activity occurs in discrete pulses within individual cells. Many feedback loops are present in the EGF receptor (EGFR)-ERK network, but the mechanisms driving pulsatile ERK kinetics are unknown. Here, we find that in cells that respond to EGF with frequency-modulated pulsatile ERK activity, stimulation through a heterologous TrkA receptor system results in non-pulsatile, amplitude-modulated activation of ERK. We further dissect the kinetics of pulse activity using a combination of FRET- and translocation-based reporters and find that EGFR activity is required to maintain ERK activity throughout the 10-20-minute lifetime of pulses. Together, these data indicate that feedbacks operating within the core Ras-Raf-MEK-ERK cascade are insufficient to drive discrete pulses of ERK activity and instead implicate mechanisms acting at the level of EGFR. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.) |
| Databáze: | MEDLINE |
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