Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The mammalian insulin-like growth factor (IGF)-II/cation-independent mannose 6-phosphate receptor (IGF2R) binds IGF-II with high affinity. By targeting IGF-II to lysosomal degradation, it plays a role in the maintenance of correct IGF-II levels in the circulation and in target tissues. Loss of IGF2R function is associated with tumor progression; therefore, the IGF2R is often referred to as a tumor suppressor. The interaction between IGF2R and IGF-II involves domains 11 and 13 of the 15 extracellular domains of the receptor. Recently, a hydrophobic binding region was identified on domain 11 of the IGF2R. In contrast, relatively little is known about the residues of IGF-II that are involved in IGF2R binding and the determinants of IGF2R specificity for IGF-II over the structurally related IGF-I. Using a series of novel IGF-II analogues and surface plasmon resonance assays, this study revealed a novel binding surface on IGF-II critical for IGF2R binding. The hydrophobic residues Phe(19) and Leu(53) are critical for IGF2R binding, as are residues Thr(16) and Asp(52). Furthermore, Thr(16) was identified as playing a major role in determining why IGF-II, but not IGF-I, binds with high affinity to the IGF2R.

Original publication

DOI

10.1074/jbc.M700531200

Type

Journal article

Journal

J Biol Chem

Publication Date

29/06/2007

Volume

282

Pages

18886 - 18894

Keywords

Amino Acid Substitution, Aspartic Acid, Binding Sites, Circular Dichroism, Humans, Hydrophobic and Hydrophilic Interactions, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Leucine, Mutagenesis, Site-Directed, Phenylalanine, Protein Folding, Protein Structure, Quaternary, Protein Structure, Tertiary, Receptor, IGF Type 2, Surface Plasmon Resonance, Threonine