Woodgett J R
Ontario Cancer Institute within the Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada.
Sci STKE. 2001 Sep 18;2001(100):re12. doi: 10.1126/stke.2001.100.re12.
As knowledge of cellular signal transduction has accumulated, general truisms have emerged, including the notion that signaling proteins are usually activated by stimuli and that they, in turn, mediate the actions of specific agonists. Glycogen synthase kinase-3 (GSK-3) is an unusual protein-serine kinase that bucks these conventions. This evolutionarily conserved protein kinase is active in resting cells and is inhibited in response to activation of several distinct pathways, including those acting by elevation of 3' phosphorylated phosphatidylinositol lipids and adenosine 3'-5'-monophosphate (cAMP). In addition, GSK-3 is distinctly regulated by, and is a core component of, the Wnt pathway. This review describes the unique characteristics of this decidedly oddball protein kinase in terms of its diverse biological functions, plethora of targets, role in several human diseases, and consequential potential as a therapeutic target.
随着细胞信号转导知识的积累，一些普遍的规律逐渐显现出来，包括信号蛋白通常被刺激激活，进而介导特定激动剂的作用。糖原合酶激酶-3（GSK-3）是一种不同寻常的蛋白丝氨酸激酶，它打破了这些常规。这种在进化上保守的蛋白激酶在静息细胞中具有活性，而在几种不同途径（包括那些通过升高3'磷酸化磷脂酰肌醇脂质和3'-5'-环磷酸腺苷（cAMP）起作用的途径）被激活时受到抑制。此外，GSK-3受到Wnt途径的独特调控，并且是该途径的核心组成部分。本综述从其多样的生物学功能、众多的靶点、在几种人类疾病中的作用以及作为治疗靶点的潜在意义等方面描述了这种极为奇特的蛋白激酶的独特特性。
