Journal
NATURE NEUROSCIENCE
Volume 7, Issue 11, Pages 1222-1232Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn1331
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Funding
- NCI NIH HHS [R01 CA107193, CA107193, R01 CA107193-03] Funding Source: Medline
- NINDS NIH HHS [NS19090, R01 NS019090] Funding Source: Medline
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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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