Role of Post Translational Modifications in Modifying the Biologic Activity of Insulin Like Growth Factor Binding Proteins
The six insulin-like growth factor binding proteins (IGFBP’s) have been shown to be produced by a variety of cell types. When present in the local pericellular microenvironment these proteins have very high affinity for insulin like factors (IGF’s) and can regulate the amount of each IGF that is available to bind to receptors. Estimates of the affinity constants for each protein show that they are at least equal to the Type l IGF receptor and in many cases significantly greater. Studies of the biologic actions of IGF-I and II in vitro in the presence of IGFBP’s have shown that the BP’s consistently inhibit the acute metabolic effects of IGF-I such as glucose transport and lipid synthesis. However, analysis of longer term effects such as stimulation of protein synthesis and DNA synthesis have shown that binding proteins can either enhance or inhibit these IGF-I actions. The major focus of research in our laboratory has been to determine if post-translational modifications of these binding proteins result in alterations in their ability to either inhibit or stimulate IGF-I actions. Studies in our lab have linked changes in several of these post-translational modifications to changes in the cellular responsiveness to IGF-I.
KeywordsSmooth Muscle Cell Culture Fibroblast Conditioned Medium Wound Breaking Strength Acute Metabolic Effect Confluent Smooth Muscle Cell
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