Insulin and Insulin-Like Growth Factor I Mediated Phosphorylations in Mouse Neuroblastoma N18 Cells: A Model for Studying Insulin and IGF-I Action on Neural Tissue
Insulin and insulin-like growth factor I are traditionally believed to regulate metabolic and growth activities in peripheral target tissues (1). However, since both peptides are present in the brain, they probably also function as neuropeptides (2). Additional evidence for their ability to function on nervous tissue is the finding that specific insulin and IGF-I receptors are present throughout the brain (3,4). These receptors exhibit structures typical of insulin and IGF-I receptors, which are heterotetramers consisting of 2 alpha-subunits which bind the ligand and two beta-subunits which are autophosphorylated as a result of ligand binding. The subunits are covalently linked via disulfide bridges (5,6,7). An important difference between brain and peripheral insulin and IGF-I receptors is the size of the receptor alpha-subunit, which has been found to be approximately lOkDa smaller in receptors from the CNS (8,9). The basis for this difference lies primarily in the extent and pattern of alpha-subunit glycosylation (10,11). Upon autophosphoryl-ation, insulin and IGF-I beta-subunits act as tyrosine kinases, toward endogenous and exogenous substrates, and considerable evidence has accumulated to suggest that this cascade of phosphorylations is critical to insulin action (12,13,14).
KeywordsInsulin Receptor Phosphoamino Acid Human Insulin Receptor Phosphoamino Acid Analysis Antiphosphotyrosine Antibody
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