Trk neurotrophin receptors

Neurotrophin-Trk receptor complexes are internalized and retrogradely transported from distal axons to the neuronal cell body where they signal to the soma to mediate target-dependent survival, growth and gene expression. The neurotrophin-Trk receptor complex is internalized by four mechanistically diverse and highly regulated pathways macropinocytosis clathrin-mediated endocytosis caveolae-mediated endocyto-sis and Pincher-mediated endocytosis. The kinase activity of Trk is probably required for receptor internalization. 

The substrates for neurotrophin Trk receptors-phos-pholipase C-y, PI3-K SHC and Grb2 adaptor proteins-are utilized by many tyrosine kinase receptors. This raises the question of how these phosphorylation events lead to different biological outcomes (Chao, 1992b). There are several possibilities. First, the strength and duration of the receptor autophosphorylation events may determine downstream signalling outcomes. Second, differential signalling may be controlled by specific dephosphorylation events. Third, there may be unique second messengers or substrates which determine the specific nature of the response. 

---