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Article
Nature Neuroscience  7, 1222 - 1232 (2004)
Published online: 17 October 2004; | doi:10.1038/nn1331

Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction

Guofa Liu1, 6, Hilary Beggs2, 6, Claudia Jürgensen1, 6, Hwan-Tae Park3, 6, Hao Tang4, Jessica Gorski5, Kevin R Jones5, Louis F Reichardt2, Jane Wu4 & Yi Rao1

1  Departments of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, Missouri 63110, USA.

2  Department of Physiology and Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.

3  Department of Physiology, College of Medicine, Dong-A University, 3-1, Dongdaesing-Dong, Seo-Gu, Pusan 602-714, South Korea.

4  Department of Pediatrics, Vanderbilt University School of Medicine, 465 21st Avenue, Nashville, Tennessee 37232, USA.

5  Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.

6  These authors contributed equally to this work.

Correspondence should be addressed to Yi Rao raoyi@pcg.wustl.edu
Although netrins are an important family of neuronal guidance proteins, intracellular mechanisms that mediate netrin function are not well understood. Here we show that netrin-1 induces tyrosine phosphorylation of proteins including focal adhesion kinase (FAK) and the Src family kinase Fyn. Blockers of Src family kinases inhibited FAK phosphorylation and axon outgrowth and attraction by netrin. Dominant-negative FAK and Fyn mutants inhibited the attractive turning response to netrin. Axon outgrowth and attraction induced by netrin-1 were significantly reduced in neurons lacking the FAK gene. Our results show the biochemical and functional links between netrin, a prototypical neuronal guidance cue, and FAK, a central player in intracellular signaling that is crucial for cell migration.

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Nature Neuroscience
ISSN: 1097-6256
EISSN: 1546-1726
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