《生命科学》 2005, 17(1): 45-48

多功能的蛋白：糖原合成酶激酶-3

毛伟峰^1，2，李 佳^2* ，袁崇刚¹

（1华东师范大学生命科学学院，上海 200062; 2中国科学院上海生命科学研究院上海药物研究所，国家新药筛选中心，上海 201203

摘　要：摘　要： 糖原合成酶激酶-3（GSK-3）是一个多功能的丝氨酸／苏氨酸类激酶，在真核生物中普遍存在。在哺乳动物中包括两个亚型，即GSK-3α 和 GSK-3β。GSK-3至少在三条细胞通路上有作用：Wnt/wingless，PI3-kinase以及Hedgehog信号通路，该酶的作用主要包括调节糖原的合成代谢，参与细胞的分化与增殖等。研究发现，GSK-3在某些疾病，如阿尔茨海默病和非胰岛素依赖型糖尿病（NIDDM）中，其活性会异常升高。现已发现了几种针对该酶的抑制剂，如aloisine，paullones和马来酰胺类化合物等。这些抑制剂的确在分子水平特异性地抑制GSK-3的活性，而对其他激酶几乎没有作用。关于这些抑制剂的研究工作也已经在细胞水平和动物模型上开展起来，为开发以GSK-3为靶点的新的治疗药物创造了良好的基础。
关键词：GSK-3；磷酸化；Wnt；抑制剂

Multi-function kinase: glycogen synthase kinase-3

MAO Wei-Feng^1，2， Li Jia^2*， YUAN Chong-Gang¹

1 College of Life Science， East China Normal University， Shanghai 200062， China; 2 National Center for Drug Screening， Shanghai Institute of Materia Medica， Shanghai Institutes for Biologicals Sciences， Chinese Academy of Sciences， Shanghai 201213， C

Abstract:
Abstract: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase， highly conserved and has been identified in every eukaryote investigated to date. It is encoded by two isoforms in mammals， termed GSK-3α and GSK-3β. GSK-3 plays an important role in at least three signal transductory systems， namely， the Wnt/wingless， Hedgehog and PI3-kinase pathways， which influence proliferation and cell survival， respectively， highlighted by the wide array of substrates controlled by this enzyme that includes cytoplasmic proteins and nuclear transcription factors. Several diseases such as in non-insulin dependent diabetes metillus (NIDDM)， Alzheimer{$39}s disease， neurological disorders， and cancer have been related to GSK-3， as a potential therapeutic target. Several new GSK-3 inhibitors， such as the aloisines， the paullones and the maleimides， have been developed. Although they are just starting to be characterized in cell culture and animal model experiments， these new inhibitors hold promise as therapeutic agents.
Key words: GSK-3; phosphorylation; Wnt; inhibitor