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Nat Neurosci. 2004 Nov;7(11):1213-21. Epub 2004 Oct 17.

Activation of FAK and Src are receptor-proximal events required for netrin signaling.

Author information

1
Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.

Abstract

The axon guidance cue netrin is importantly involved in neuronal development. DCC (deleted in colorectal cancer) is a functional receptor for netrin and mediates axon outgrowth and the steering response. Here we show that different regions of the intracellular domain of DCC directly interacted with the tyrosine kinases Src and focal adhesion kinase (FAK). Netrin activated both FAK and Src and stimulated tyrosine phosphorylation of DCC. Inhibition of Src family kinases reduced DCC tyrosine phosphorylation and blocked both axon attraction and outgrowth of neurons in response to netrin. Mutation of the tyrosine phosphorylation residue in DCC abolished its function of mediating netrin-induced axon attraction. On the basis of our observations, we suggest a model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling.

PMID:
15494734
PMCID:
PMC2373267
DOI:
10.1038/nn1329
[Indexed for MEDLINE]
Free PMC Article

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