10         20         30         40         50         60
         |          |          |          |          |          |
MTPHRLLPPL LLLLALLLAA SPGGALARCP GCGQGVQAGC PGGCVEEEDG GSPAEGCAEA - 60
EGCLRREGQE CGVYTPNCAP GLQCHPPKDD EAPLRALLLG RGRCLPARAP AVAEENPKES - 120
KPQAGTARPQ DVNRRDQQRN PGTSTTPSQP NSAGVQDTEM GPCRRHLDSV LQQLQTEVYR - 180
GAQTLYVPNC DHRGFYRKRQ CRSSQGQRRG PCWCVDRMGK SLPGSPDGNG SSSCPTGSSG - 240

Insulin-like growth factors (IGF-I and -II) are widely expressed polypeptides that promote cell proliferation, differentiation and survival by endocrine, paracrine and autocrine mechanisms. The IGF system is the major control pathway of physiological growth in mammals. IGF actions are finely regulated by a family of six high-affinity IGF binding proteins (IGFBPs 1-6). These IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. IGFBP-6 differs functionally from other IGFBPs in binding IGF-II with 20-100 fold higher affinity than IGF-I, whereas IGFBPs 1-5 do not have a marked IGF binding preference. IGFBPs consist of three domains of approximately equal size, with both the N- and C-domains of IGFBPs being implicated in high-affinity IGF binding.