What's new in the IGF-binding proteins?

Since their initial discovery over 25 years ago as IGF carrier proteins, the insulin-like growth factor binding protein (IGFBP) family has grown to six members, ranging in size from 216 to 289 amino acids. The assumption over the years has been that this family of proteins, having higher affinities for IGF-I and IGF-II than does the IGF-IR, serves to block access of these ligands to the receptor. Although the need for such regulatory proteins is consistent with the constitutive secretion of IGFs from many cell types, it is not surprising that additional functions have begun to be uncovered for these proteins. This review will examine new and old actions of the IGFBPs from a biochemical and cell biological perspective.