Horm Metab Res 1999; 31(2/03): 226-234
DOI: 10.1055/s-2007-978723
© Georg Thieme Verlag Stuttgart · New York

Insulin-Like Growth Factor Binding Protein-6: The “Forgotten” Binding Protein?

L. A. Bach
  • University of Melbourne, Department of Medicine, Austin & Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia
Further Information

Publication History

1998

1998

Publication Date:
19 April 2007 (online)

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. IGEBP-6 is O-glycolsylated, and five serine/threonine glycosylation sites in the non-conserved mid-region of human IGEBP-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.

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