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

Research output: Contribution to journalArticle

180 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 languageEnglish (US)
Pages (from-to)1204-1212
Number of pages9
JournalNature Neuroscience
Volume7
Issue number11
DOIs
StatePublished - Nov 2004

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ren, X. R., Ming, G. L., Xie, Y., Hong, Y., Sun, D. M., Zhao, Z. Q., Feng, Z., Wang, Q., Shim, S., Chen, Z. F., Song, H. J., Mei, L., & Xiong, W. C. (2004). Focal adhesion kinase in netrin-1 signaling. Nature Neuroscience, 7(11), 1204-1212. https://doi.org/10.1038/nn1330