Insulin‐like growth factor binding proteins: a proposed superfamily

Hwa V, Oh Y, Rosenfeld RG. Insulin‐like growth factor binding proteins: a proposed superfamily. Acta Pzdiatr 1999; Suppl 428:37‐45. Stockholm. ISSN 0803‐5326 The conventional concept is that the insulin‐like growth factor binding proteins (IGFBPs) are cysteine‐rich proteins, with conserved N‐ and C‐domains, that are capable of binding insulin‐like growth factors (IGFs) with high affinity. This dogma was recently challenged by the discovery of a group of cysteine‐rich proteins that share important structural similarities with the IGFBPs, but have demonstrably lower affinity for IGFs. It is therefore proposed that these IGFBP‐related proteins (IGFBP‐rPs) and the IGFBPs constitute an IGFBP superfamily. We speculate that the IGFBP superfamily is derived from an ancestral gene/protein that was critically involved in the regulation of cell growth and was capable of binding IGF peptides. Over the course of evolution, some members (IGFBPs) evolved into high‐affinity IGF binders and others (IGFBP‐rPs) into low‐affinity IGF binders, thereby conferring on the IGFBP superfamily the ability to influence cell growth by both IGF‐dependent and IGF‐independent means. 0 Insulin‐like growth factor binding protein, insulin‐like growth factor binding protein‐related protein, superfamily