Focal adhesion kinase in netrin-1 signaling |
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Authors: | Ren Xiu-Rong Ming Guo-Li Xie Yi Hong Yan Sun Dong-Mei Zhao Zhong-Qiu Feng Zhu Wang Qiang Shim Sangwoo Chen Zhou-Feng Song Hong-Jun Mei Lin Xiong Wen-Cheng |
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Affiliation: | Department of Pathology, University of Alabama, Birmingham, Alabama 35294, USA. |
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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. |
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