Insulin-like growth factor binding protein-6: the "forgotten" binding protein?
Insulin-like growth factor binding protein-6 (IGFBP-6) differs from IGFBPs 1-5 in that it binds IGF-II with marked preferential affinity over IGF-I. Human and rat IGFBP-6 lack 2 and 4 N-terminal cysteines and therefore the Gly-Cys-Gly-Cys-Cys motif present in IGFBPs 1-5. IGFBP-6 is O-glycolsylated, and five serine/threonine glycosylation sites in the non-conserved mid-region of human IGFBP-6 have been identified. O-Glycosylation inhibits proteolysis of IGFBP-6 by chymotrypsin and trypsin, but has no effect on high affinity IGF binding. IGFBP-6 is a relatively specific inhibitor of IGF-II actions; it has not been shown to potentiate IGF actions. IGFBP-6 is only cell-associated to a very limited extent, if at all. IGFBP-6 is often expressed in non-proliferative, quiescent states in vitro and differentiating agents increase its expression. IGFBP-6 expression is associated with inhibition of growth of tumour cells in vitro and in vivo. Although many questions remain regarding the biological role of IGFBP-6, its major function appears to be the regulation of IGF-II actions. This could be especially significant since IGF-II has been implicated as an autocrine tumour growth factor.
Bach
L A
LA
University of Melbourne, Department of Medicine, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia. bach@austin.unimelb.edu.au
D000595:Amino Acid Sequence; D000818:Animals; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data
D018976:Insulin-Like Growth Factor Binding Protein 6