| 背景： | Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase with two isoforms (alpha and beta), was originally discovered as a key enzyme in glycogen metabolism. GSK-3 was subsequently shown to function in cell division, proliferation, motility and survival. GSK-3 plays a role in a number of pathological conditions including cancer and diabetes and is increasingly seen as an important component of neurological diseases. GSK-3 phosphorylates tau and presenilin-1, which are involved in the development of Alzheimer's disease. Both isoforms of GSK-3 are ubiquitously expressed, although particularly high levels of GSK-3beta are found in the brain where it is involved in synaptic plasticity, possibly via regulation of NMDA receptor trafficking. GSK-3 phosphorylates over 40 different substrates including signaling proteins, transcription factors and structural proteins, and is part of the signal transductioncascade of a large number of growth factors and cytokines. The activity of GSK is regulated by phosphorylation (Akt: Akt-mediated phosphorylation at Ser21 of GSK-3? and Ser9 of GSK-3?, S6K, RSK, PKA and PKC), dephosphorylation (PP1 and PP2A), and by binding to protein complexes (with beta-catenin, axin, CK1 and the APC complex).REFERENCES1. EMBO J. 1998 Mar 2;17(5):1371-84.2. Curr Biol. 2001 Jan 9;11(1):44-9.3. Cancer Lett. 2003 Sep 25;199(2):201-8. |
