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First published online December 21, 2005

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The FAKs about axon guidance

Axonal guidance molecules guide the growth of neuronal axons to their targets during the development of the nervous system. The guidance molecule netrin has two receptors: DCC transduces attractive signals, whereas UNC5 (alone or together with DCC) transduces repulsive signals. The signalling pathways downstream of UNC5 and DCC are poorly understood. Now, Kun-Liang Guan and colleagues report that netrin stimulates tyrosine phosphorylation of UNC5 in a DCC-dependent manner, and this involves recruitment of focal adhesion kinase (FAK) and Src (see p. 47). The authors show that netrin induces UNC5 phosphorylation in cultured mouse neurons and that DCC stimulates this. Other experiments indicate that Src and FAK can each phosphorylate UNC5 in vitro but both tyrosine kinases are needed to stimulate UNC5 phosphorylation efficiently in vivo. The authors propose that activation of the DCC-UNC5 receptor complex by netrin causes the recruitment and activation of Src and FAK, which tyrosine phosphorylate UNC5 to create binding sites for the downstream signalling molecules that generate a repulsive signal in response to netrin.

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Related articles in JCS:

FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5

Weiquan Li, Jennifer Aurandt, Claudia Jürgensen, Yi Rao, and Kun-Liang Guan
JCS 2006 119: 47-55. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?