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


ABSTRACT: 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.

SUBMITTER: Liu G 

PROVIDER: S-EPMC2266630 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature

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

Liu Guofa G   Beggs Hilary H   Jürgensen Claudia C   Park Hwan-Tae HT   Tang Hao H   Gorski Jessica J   Jones Kevin R KR   Reichardt Louis F LF   Wu Jane J   Rao Yi Y  

Nature neuroscience 20041017 11


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 outgro  ...[more]

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