Keeping IGF-II under control: lessons from the IGF-II-IGF2R crystal structure.
Insulin-like growth factor-II (IGF-II) is a key regulator of cell growth, survival, migration and differentiation. Its pivotal role in these processes requires tight regulation of both expression and activity. The type 1 IGF receptor tyrosine kinase (IGF-1R) mediates IGF-II actions, and a family of six high affinity IGF binding proteins (IGFBPs) regulates IGF-II circulating half-life and its availability to bind IGF-1R. In addition, the type 2 IGF receptor (IGF2R; also called the cation-independent mannose-6-phosphate receptor) modulates the circulating and tissue levels of IGF-II by targeting it to lysosomes for degradation. The recently elucidated crystal structure of IGF-II-IGF2R complex provides new insight into IGF-II regulation, and reveals a common binding surface on IGF-II for the regulatory proteins, IGF2R and the IGFBPs.
Cancer Research UK Receptor Structure Research Group, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK.
James
J
Brown
E Yvonne
EY
Jones
Briony E
BE
Forbes
D000818:Animals; D001665:Binding Sites; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000378:metabolism*
D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II