Focal adhesion kinase in netrin-1 signaling

被引：181

作者：

Ren, XR

Ming, GL

Xie, Y

Hong, Y

Sun, DM

Zhao, ZQ

Feng, Z

Wang, Q

Shim, S

Chen, ZF

Song, HJ

Mei, L

Xiong, WC ^{[1
]}

机构：

[1] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA

[4] Washington Univ, Sch Med Pain Ctr, Dept Anesthesiol, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med Pain Ctr, Dept Psychiat, St Louis, MO 63110 USA

[6] Washington Univ, Sch Med Pain Ctr, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA

[7] Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA

[8] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA

[9] Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA

[10] Univ Alabama, Dept Phys Med & Rehabil, Birmingham, AL 35294 USA

来源：

NATURE NEUROSCIENCE | 2004年 / 7卷 / 11期

关键词：

D O I：

10.1038/nn1330

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1204 / 1212

页数：9

共 51 条

[1] The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein [J].