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.
Trends Biochem Sci. 2009 Dec;34(12):612-9. doi: 10.1016/j.tibs.2009.07.003. Epub 2009 Sep 30.
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.
胰岛素样生长因子-II（IGF-II）是细胞生长、存活、迁移和分化的关键调节因子。它在这些过程中的关键作用需要对其表达和活性进行严格的调节。1 型胰岛素样生长因子受体酪氨酸激酶（IGF-1R）介导 IGF-II 的作用，而六类高亲和力 IGF 结合蛋白（IGFBPs）调节 IGF-II 的循环半衰期及其与 IGF-1R 结合的可用性。此外，2 型胰岛素样生长因子受体（IGF2R；也称为阳离子非依赖性甘露糖-6-磷酸受体）通过将 IGF-II 靶向溶酶体进行降解，来调节 IGF-II 的循环和组织水平。最近阐明的 IGF-II-IGF2R 复合物晶体结构为 IGF-II 的调节提供了新的见解，并揭示了 IGF-II 与调节蛋白 IGF2R 和 IGFBPs 的共同结合表面。
