Details:

Alternative Title:
PLoS One
Publisher's site:
http://dx.doi.org/10.1371/journal.pone.0092917
Personal Author:
Zhang, Kai ; Duan, Liting ; Ong, Qunxiang ; Lin, Ziliang ; Varman, Pooja Mahendra ; ... More +
Zhang, Kai ; Duan, Liting ; Ong, Qunxiang ; Lin, Ziliang ; Varman, Pooja Mahendra ; Sung, Kijung ; Cui, Bianxiao Less -
Description:
It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network.
Subject:
[+]
Animals
Cell Differentiation
Cell Membrane
Cryptochromes
Dose-Response Relationship, Radiation
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases
Kinetics
Light
MAP Kinase Kinase Kinases
MAP Kinase Signaling System
Mice
Nerve Growth Factor
Neurites
NIH 3T3 Cells
PC12 Cells
Protein Structure, Tertiary
Protein Transport
Raf Kinases
Rats

Source:
PLoS One. 2014; 9(3).
Pubmed ID:
24667437
Pubmed Central ID:
PMC3965503
Document Type:
Journal Article
Funding:
DP2-NS082125/DP/NCCDPHP CDC HHS/United States
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:00010abb02df853243b542aa96db21eae6bf2d8e6ff9678ec9b744725b933944
File Type:

Supporting Files

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