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Science
Article
Data sources: UnpayWall
Science
Article . 2008 . Peer-reviewed
Data sources: Crossref
Science
Article . 2008
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Design Logic of a Cannabinoid Receptor Signaling Network That Triggers Neurite Outgrowth

Authors: Kenneth D, Bromberg; Avi, Ma'ayan; Susana R, Neves; Ravi, Iyengar;

Design Logic of a Cannabinoid Receptor Signaling Network That Triggers Neurite Outgrowth

Abstract

Cannabinoid receptor 1 (CB1R) regulates neuronal differentiation. To understand the logic underlying decision-making in the signaling network controlling CB1R-induced neurite outgrowth, we profiled the activation of several hundred transcription factors after cell stimulation. We assembled an in silico signaling network by connecting CB1R to 23 activated transcription factors. Statistical analyses of this network predicted a role for the breast cancer 1 protein BRCA1 in neuronal differentiation and a new pathway from CB1R through phosphoinositol 3-kinase to the transcription factor paired box 6 (PAX6). Both predictions were experimentally confirmed. Results of transcription factor activation experiments that used pharmacological inhibitors of kinases revealed a network organization of partial OR gates regulating kinases stacked above AND gates that control transcription factors, which together allow for distributed decision-making in CB1R-induced neurite outgrowth.

Related Organizations
Keywords

Homeodomain Proteins, Neurons, PAX6 Transcription Factor, BRCA1 Protein, Computational Biology, Cell Differentiation, Hippocampus, Rats, Mice, Phosphatidylinositol 3-Kinases, Receptor, Cannabinoid, CB1, Cell Line, Tumor, Protein Interaction Mapping, Neurites, Animals, Paired Box Transcription Factors, Computer Simulation, Eye Proteins, Cells, Cultured, Metabolic Networks and Pathways

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    130
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
130
Top 10%
Top 10%
Top 1%
bronze
Related to Research communities
Cancer Research