Focal adhesion kinase in netrin-1 signaling

@article{Ren2004FocalAK,
  title={Focal adhesion kinase in netrin-1 signaling},
  author={Xiu-rong Ren and Guo-li Ming and Yi Xie and Yan Hong and Dong Sun and Zhong-qiu Zhao and Zhu Feng and Qiang Wang and Sangwoo Shim and Zhou-Feng Chen and Hong-jun Song and Lin Mei and Wen-Cheng Xiong},
  journal={Nature Neuroscience},
  year={2004},
  volume={7},
  pages={1204-1212}
}
Netrins are a family of secreted molecules that are important for axonal outgrowth and guidance in the developing nervous system. However, the signaling mechanisms that lie immediately downstream of netrin receptors remain poorly understood. Here we report that the netrin receptor DCC (deleted in colorectal cancer) interacts with the focal adhesion kinase (FAK), a kinase implicated in regulating cell adhesion and migration. FAK was expressed in developing brains and was localized with DCC in… 
Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction
TLDR
The results show the biochemical and functional links between netrin, a prototypical neuronal guidance cue, and FAK, a central player in intracellular signaling that is crucial for cell migration.
Activation of FAK and Src are receptor-proximal events required for netrin signaling
TLDR
A model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling is suggested.
DCC-dependent Phospholipase C Signaling in Netrin-1-induced Neurite Elongation*
TLDR
Evidence that netrin-1 stimulates phosphatidylinositol bisphosphate hydrolysis in cortical neurons is provided and a crucial role of PLC signaling is demonstrated in netin-1-induced neurite elongation in cortex.
Tyrosine Phosphorylation of Netrin Receptors in Netrin-1 Signaling
TLDR
This paper shows that both DCC and neogenin become tyrosine phosphorylated in cortical neurons in response to netrin-1, and shows that inhibition of Src family kinase activity attenuated netin-1-induced neurite outgrowth.
p130CAS Is Required for Netrin Signaling and Commissural Axon Guidance
TLDR
It is reported that netrin-1 induces tyrosine phosphorylation of p130CAS (Crk-associated substrate), which is a key component in the netrin signal transduction pathway and plays an important role in guiding commissural axons in vivo.
Netrin-1 Attracts Axons through FAK-Dependent Mechanotransduction
TLDR
An important role for mechanotransduction during chemoattraction to netrin-1 is demonstrated and that mechanical activation of FAK reinforces interactions with netrin -1 allowing greater forces to be exerted.
FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5
TLDR
The data suggest a model in which netrin stimulates UNC5 tyrosine phosphorylation and signaling in a manner dependent on the co-receptor DCC, through the recruitment of Src and FAK kinases.
Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B
TLDR
It is shown that netrin-1 induces interaction of UNC5B with the brain-specific GTPase PIKE-L, which triggers the activation of PtdIns-3-OH kinase signalling, prevents UNC5B's pro-apoptotic activity and enhances neuronal survival.
Netrins: versatile extracellular cues with diverse functions
TLDR
The mechanisms involved in netrin signalling in vertebrate and invertebrate systems are reviewed and the functions ofNetrin signalling during the development of neural and non-neural tissues are discussed.
The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation
TLDR
It is shown that Netrin-1 ligand binding to Neogenin-1 leads to FAK autophosphorylation and integrin β1 activation in a FAK dependent manner, thus promoting neuroblastoma cell migration.
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References

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Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction
TLDR
The results show the biochemical and functional links between netrin, a prototypical neuronal guidance cue, and FAK, a central player in intracellular signaling that is crucial for cell migration.
Activation of FAK and Src are receptor-proximal events required for netrin signaling
TLDR
A model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling is suggested.
Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation
TLDR
It is shown that Dcc activates mitogen-activated protein kinase (MAPK) signalling, by means of extracellular signal-regulated kinases (ERK)-1 and -2, on netrin-1 binding in both transfected cells and commissural neurons, which contributes to netrin signalling in axon growth and guidance.
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