Focal adhesion kinase in netrin-1 signaling

Xiu Rong Ren; Guo Li Ming; Yi Xie; Yan Hong; Dong Mei Sun; Zhong Qiu Zhao; Zhu Feng; Qiang Wang; Sangwoo Shim; Zhou Feng Chen; Hong Jun Song; Lin Mei; Wen Cheng Xiong

doi:10.1038/nn1330

Focal adhesion kinase in netrin-1 signaling

Xiu Rong Ren, Guo Li Ming, Yi Xie, Yan Hong, Dong Mei Sun, Zhong Qiu Zhao, Zhu Feng, Qiang Wang, Sangwoo Shim, Zhou Feng Chen, Hong Jun Song, Lin Mei, Wen Cheng Xiong

Graduate Studies

Research output: Contribution to journal › Article › peer-review

190 Scopus citations

Abstract

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 cultured neurons. Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth and attractive growth cone turning. Taken together, these results indicate a new signaling mechanism for DCC, in which FAK is activated upon netrin-1 stimulation and mediates netrin-1 function; they also identify a critical role for FAK in axon navigation.

Original language	English (US)
Pages (from-to)	1204-1212
Number of pages	9
Journal	Nature Neuroscience
Volume	7
Issue number	11
DOIs	https://doi.org/10.1038/nn1330
State	Published - Nov 2004

ASJC Scopus subject areas

General Neuroscience

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nn1330

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title = "Focal adhesion kinase in netrin-1 signaling",

abstract = "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 cultured neurons. Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth and attractive growth cone turning. Taken together, these results indicate a new signaling mechanism for DCC, in which FAK is activated upon netrin-1 stimulation and mediates netrin-1 function; they also identify a critical role for FAK in axon navigation.",

author = "Ren, {Xiu Rong} and Ming, {Guo Li} and Yi Xie and Yan Hong and Sun, {Dong Mei} and Zhao, {Zhong Qiu} and Zhu Feng and Qiang Wang and Sangwoo Shim and Chen, {Zhou Feng} and Song, {Hong Jun} and Lin Mei and Xiong, {Wen Cheng}",

note = "Funding Information: We are grateful to Y. Rao (Washington University), D. Ilic (University of California at San Francisco) and B. Vogelstein (Johns Hopkins Medical School) for reagents. We thank L. Xu (University of Alabama at Birmingham) for help on statistical analyses. G.L.M. is partially supported by Charles E. Culpeper Scholarships in Medical Science and the National Institutes of Health (NIH). This study is supported by grants from the NIH to Z.F.C., L.M., and W.C.X.",

year = "2004",

month = nov,

doi = "10.1038/nn1330",

language = "English (US)",

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T1 - Focal adhesion kinase in netrin-1 signaling

AU - Ren, Xiu Rong

AU - Ming, Guo Li

AU - Xie, Yi

AU - Hong, Yan

AU - Sun, Dong Mei

AU - Zhao, Zhong Qiu

AU - Feng, Zhu

AU - Wang, Qiang

AU - Shim, Sangwoo

AU - Chen, Zhou Feng

AU - Song, Hong Jun

AU - Mei, Lin

AU - Xiong, Wen Cheng

N1 - Funding Information: We are grateful to Y. Rao (Washington University), D. Ilic (University of California at San Francisco) and B. Vogelstein (Johns Hopkins Medical School) for reagents. We thank L. Xu (University of Alabama at Birmingham) for help on statistical analyses. G.L.M. is partially supported by Charles E. Culpeper Scholarships in Medical Science and the National Institutes of Health (NIH). This study is supported by grants from the NIH to Z.F.C., L.M., and W.C.X.

PY - 2004/11

Y1 - 2004/11

N2 - 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 cultured neurons. Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth and attractive growth cone turning. Taken together, these results indicate a new signaling mechanism for DCC, in which FAK is activated upon netrin-1 stimulation and mediates netrin-1 function; they also identify a critical role for FAK in axon navigation.

AB - 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 cultured neurons. Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth and attractive growth cone turning. Taken together, these results indicate a new signaling mechanism for DCC, in which FAK is activated upon netrin-1 stimulation and mediates netrin-1 function; they also identify a critical role for FAK in axon navigation.

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Focal adhesion kinase in netrin-1 signaling

Abstract

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