Insulin-like growth factor binding proteins and their role in controlling IGF actions.
The insulin-like growth factor binding proteins (IGFBPs) are a family of six proteins that bind to insulin-like growth factor-I and -II with very high affinity. Because their affinity constants are between two- and 50-fold greater than the IGF-I receptor, they control the distribution of the IGFs among soluble IGFBPs in interstitial fluids, IGFBPs bound to cell surfaces or extracellular matrix (ECM) and cell surface receptors. Although there are six forms of insulin-like growth factor binding proteins, most interstitial fluids contain only three or four forms, and usually only one or two predominate. The proteins differ significantly in their biochemical characteristics, and this accounts for many of the differences that have been observed in their biological actions. Several different types of protease cleave these binding proteins. Proteolytic cleavage generally inactivates the binding proteins or reduces their ability to bind to IGF-I or -II substantially. Several cell types have been shown to secrete these proteases; therefore, the factors that regulate protease activity can control binding protein actions indirectly. Other post-translational modifications, such as glycosylation and phosphorylation, have been shown to alter IGF binding protein activity. While binding protein actions have been studied extensively in vitro, many of the in vivo activities of these proteins remain to be defined.
Clemmons
D R
DR
Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill 27599, USA.
D000595:Amino Acid Sequence; D000818:Animals; D004702:Endocrine Glands / Q000502:physiology; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid
D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II