Tyrosine 981, a novel ret autophosphorylation site, binds c-Src to mediate neuronal survival.

摘要: The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are factors that influence several aspects of the developing and injured nervous system. GFLs signal through a common receptor tyrosine kinase (Ret) one four ligand-binding co-receptors (GFRα1 to 4). Ligand-induced translocation Ret lipid rafts, where it interacts with nonreceptor Src, is prerequisite for full biological activity these factors. This interaction subsequent activation Src required GFL-mediated neuronal survival, neurite outgrowth, or proliferation. Here we show by multiple approaches 981 constitutes major binding site homology 2 domain therefore primary residue responsible upon engagement. Other tyrosines such as 1015 1029 may contribute overall between judged overexpression experiments. By generating phosphospecific antibody, demonstrate novel autophosphorylation in Ret. Importantly, also this becomes phosphorylated dissociated sympathetic neurons after ligand stimulation. Mutation phenylalanine reduces GDNF-mediated survival transfected cerebellar granule neuron paradigm.