The insulin-like growth factor binding protein superfamily: New perspectives

Ron G. Rosenfeld, Vivian Hwa, Lisa Wilson, Abel Lopez-Bermejo, Caroline Buckway, Christine Burren, Won Kyu Choi, Gayathri Devi, Angela Ingermann, Donna Graham, Giuseppi Minniti, Anna Spagnoli, Youngman Oh

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


The insulin-like growth factor (IGF) binding proteins (IGFBPs) were initially identified as carrier proteins for IGF-I and IGF-II in a variety of biologic fluids. Their presumed function was to protect IGF peptides from degradation and clearance, increase the half-life of the IGFs, and deliver them to appropriate tissue receptors. The concept of IGFBPs as simple carrier proteins has been complicated, however, by a number of observations: 1) the six IGFBPs vary in their tissue expression and their regulation by other hormones and growth factors; 2) the IGFBPs are subjected to proteolytic degradation, thereby altering their affinities for the IGFs; 3) IGFBP-3 and IGFBP-5, in addition to binding IGFs, also can associate with an acid-labile subunit, thereby increasing further the half-life of the IGFs; 4) in addition to modifying the access of IGF peptides to IGF and insulin receptors, several of the IGFBPs may be capable of increasing IGF action; 5) some of the IGFBPs may be capable of IGF-independent regulation of cell growth; 6) some of the IGFBPs are associated with cell membranes or possibly with membrane receptors; and 7) some of the IGFBPs have nuclear recognition sites and may be found within the nucleus. Additionally, a number of cDNAs identified recently have been found to encode proteins that bind IGFs, but with substantially lower affinities than is the case with IGFBPs. The N-terminal regions of the predicted proteins are structurally homologous to the classic IGFBPs, with conservation of the cysteine-rich region. These observations suggest that these low-affinity binders are members of an IGFBP superfamily, capable of regulating cell growth by both IGF-dependent and IGF-independent mechanisms.

Original languageEnglish (US)
Pages (from-to)1018-1020
Number of pages3
Issue number4 II
StatePublished - Oct 1999
Externally publishedYes


  • Insulin-like growth factor
  • Insulin-like growth factor binding proteins

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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