期刊
SCIENCE
卷 361, 期 6405, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aao3048
关键词
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资金
- Arnold O. Beckman Postdoctoral Fellowship
- European Molecular Biology Organization [ALTF 419-2010]
- UCSF Program for Breakthrough Biomedical Research Postdoctoral Research Award
- NIH [DP2EB024247, DP2 CA174497, R01CA169338, R01CA204302, R01CA211052, P50GM081879, R01GM55040]
- St. Baldrick's Foundation
- Damon Runyon-Sohn Foundation fellowship [6P-13]
- Howard Hughes Medical Institute
- Pew and Stewart Foundations
The Ras-Erk (extracellular signal-regulated kinase) pathway encodes information in its dynamics; the duration and frequency of Erk activity can specify distinct cell fates. To enable dynamic encoding, temporal informationmust be accurately transmitted from the plasma membrane to the nucleus. We used optogenetic profiling to show that both oncogenic B-Raf mutations and B-Raf inhibitors can cause corruption of this transmission, so that short pulses of input Ras activity are distorted into abnormally long Erk outputs. These changes can reshape downstream transcription and cell fates, resulting in improper decisions to proliferate. These findings illustrate how altered dynamic signal transmission properties, and not just constitutively increased signaling, can contribute to cell proliferation and perhaps cancer, and how optogenetic profiling can dissect mechanisms of signaling dysfunction in disease.
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