Activation of FAK and Src are receptor-proximal events required for netrin signaling. Nat Neurosci 2004 Nov;7(11):1213-21
Date
10/21/2004Pubmed ID
15494734Pubmed Central ID
PMC2373267DOI
10.1038/nn1329Scopus ID
2-s2.0-7044260519 (requires institutional sign-in at Scopus site) 206 CitationsAbstract
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.
Author List
Li W, Lee J, Vikis HG, Lee SH, Liu G, Aurandt J, Shen TL, Fearon ER, Guan JL, Han M, Rao Y, Hong K, Guan KLMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
Brain
Cell Adhesion Molecules
Cell Line
Chickens
DCC Receptor
Drug Interactions
Embryo, Mammalian
Embryo, Nonmammalian
Enzyme Activation
Enzyme Inhibitors
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Growth Cones
Humans
Immunoprecipitation
Larva
Microinjections
Mutagenesis
Nerve Growth Factors
Netrin-1
Neurons
Phosphorylation
Protein Structure, Tertiary
Protein-Tyrosine Kinases
Pyrimidines
Receptors, Cell Surface
Signal Transduction
Spinal Cord
Time Factors
Transfection
Tumor Suppressor Proteins
Tyrosine
Xenopus
src-Family Kinases
