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.
Key words
Insulin-Like Growth Factor - Binding Protein - Glycosylation
