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Insulin action initiated by insulin binding to its cognate receptor is performed via phosphorylation of tyrosines on substrate proteins by the receptor tyrosine kinase domain. This process involves autophosphorylation of tyrosine residues in the cytoplasmic domain of the receptor. A comparable action is mediated by nerve growth factor (NGF) and epidermal growth factor (EGF) receptors. Few articles have been directed to the morphological regional distribution in the brain of phosphotyrosine, using antibodies. The first extensive description that proved a topographical distribution for phosphotyrosine in the rat brain was conducted by Marani and Maassen. It was shown that alternating areas positive and negative for phosphotyrosine could be described. These areas showed different localizations that were in good agreement with the biochemical results obtained by others. Moreover, fetal and postnatal series confirmed the results that phosphotyrosine content is extremely high in the developing brain as compared to the mature brain. In the mature brain, the phosphotyrosine localization is also found in the neuropil, not only in neurons. High concentrations of phosphotyrosine in a regional distribution are found in the rat rhinencephalon, the cortex, the basal ganglia (mainly in neostriatum and substantia nigra), hypothalamus and the habenular nuclei. In the hippocampus, the positivity for phosphotyrosine can be detected in the pyramidal cells and the neuropil. The hippocampal subdivisions of CA1 and CA3 can be weakly discerned. Topographical studies of the distribution of insulin receptor substrate-1 (IRS-1), growth factor receptor-bound protein-2 (GRB-2) or its adaptor molecule and substrate of insulin receptor kinase (She) that complexes to GRB-2 and conducts insulin action towards the Ras complex are absent for the brain. Biomedical Reviews 1996; 5: 73-82.

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Detection of phosphotyrosine, insulin receptor substrate-1 and growth factor receptor-bound protein-2 in the magnocellular forebrain system and hypothalamus of cat and man