Phosphorylation of insulin-like growth factor binding proteins.
Insulin-like growth factor (IGF) binding proteins (IGFBPs) play a key role in regulating the availability of IGFs in the circulation and the extracellular environment. Three of these proteins-IGFBP-1, IGFBP-3 and IGFBP-5-are known to be serine-phosphorylated in their central domains, and the others have possible target sites for serine/threonine kinases. Whereas nonphosphorylated IGFBP-1 may potentiate IGF action in certain cells, phosphorylation increases its affinity for IGFs, and converts the protein to an inhibitory form. The highly phosphorylated protein predominates in the circulation, where it may acutely regulate IGF bioavailability. IGFBP-3 is also secreted as a phosphoprotein, and can be phosphorylated in vitro by protein kinases A and C, and casein kinase II. De-phosphorylation has no effect on IGF-binding, but may increase its ability to bind to the acid-labile subunit and to associate with cell surfaces. Although no specific functions have yet been ascribed to phosphorylated forms of the other IGFBPs, current evidence supports the proposal that IGFBP phosphorylation plays an important role in the regulation of IGFBP function.
Coverley
J A
JA
Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW, Australia. coverley@blackburn.su.med.oz.au
Baxter
R C
RC
D000818:Animals; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D010768:Phosphoserine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases