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.
Brown
James
J
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.
Jones
E Yvonne
EY
Forbes
Briony E
BE
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