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      IGF binding proteins: regulation of cellular actions.

      Growth regulation

      Models, Chemical, Insulin-Like Growth Factor Binding Proteins, Humans, physiology, chemistry, Carrier Proteins, Animals

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          Abstract

          The recent purification and structural analysis of the six forms of insulin-like growth factor binding proteins has opened up the possibility of studying their mechanism of action at the cellular level. While a great deal of information has been published regarding control of secretion of these proteins by cells, their modulation of the target cell actions of the IGFs remains incompletely studied. Both IGFBP-1 and 3 have been shown to be bipotential regulators. Using one set of culture conditions, both proteins appear to inhibit IGF-mediated growth while if other conditions are used they appear to stimulate growth. IGFBP-2, 5 and 6 have been less well studied in this regard, although several studies showing growth inhibition with IGFBP-2 have been published. IGFBP-4 appears to be consistently inhibitory and no studies showing stimulation have been published to date. Recent research has focused on the reason for these bifunctional effects. Clearly the ability to adhere to cell surfaces appears to be one important property of these proteins that results in their ability to potentiate or inhibit growth. Likewise, phosphorylation of IGFBP-1 on serine residues appears to be a structurally modifying change which results in altered growth regulation. The future will no doubt uncover other post-translational modifications that result in modulation of biologic activity.

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          1283101

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