| Neurotrophins are target-derived factors, which play critical roles in the survival, differentiation and the maintenance of neurons in both peripheral and central nervous system. Besides nerve growth factor (NGF), in mammals, the family of neurotrophins includes brain-derived neurotrophic factor (BDNF), neruotrophin-3 (NT-3), neruotrophin-4/5(NT-4/5). The effects of NGF are mediated by two different membrane receptors: the receptor tyrosine kinase TrkA and p75NTR. After binding with TrkA, NGF would trigger the homologous dimerization and autophosphorylation of TrkA and activate the downstream signaling pathway such as Ras-Raf-MAPK, PI3-K and PLCγ. TrkA, belonging to the receptor kinase family, is a transmembrane glycoprotein with extracellular domains for lingand-binding, transmembrane region and intracellular domains with the tyrosine kinase activity. The intracellular domain of TrkA provides the docking sites, most of them with tyrosine residues such as Y499, Y547, Y638, Y634, for many adaptor proteins including Shc, Grb2, SH2-B, etc., which are important for intracellular signaling.Mint family includes three members: Mintl, Mint2, Mint3, also called XI la, X11β and X 11γ, which has multiple functional model-domains. The Mints share high homology at their carboxy-termini where they contain PTB (phosphorylated-tyrosine binding) domains and also two PDZ (postsynaptic density-95, disc-large turmour suppressor gene, zona occludens-1) domains, but diverge towards their amino-termini. Mints play roles in the transmitter release of the synaptic vesicles and the metabolism of β-APP through binding different molecules including muncl8-l, Cask, APP, NF-k B/p65, presenile-1, ect., with their PTB or PDZ domains.We have previously demonstrated that the intracellular domain of TrkA could bind to Mint2 in vitro and in vivo by using yeast two-hybrid system, co-immuno-precipitation and GST-pull down assays. In the present study, we sought to investigate...
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