Standen C L, Brownlees J, Grierson A J, Kesavapany S, Lau K F, McLoughlin D M, Miller C C
Department of Neuroscience, Institute of Psychiatry, Kings College, London, UK.
J Neurochem. 2001 Jan;76(1):316-20. doi: 10.1046/j.1471-4159.2001.00102.x.
Threonine(668) (thr(668)) within the carboxy-terminus of the Alzheimer's disease amyloid precursor protein (APP) is a known in vivo phosphorylation site. Phosphorylation of APPthr(668) is believed to regulate APP function and metabolism. Thr(668) precedes a proline, which suggests that it is targeted for phosphorylation by proline-directed kinase(s). We have investigated the ability of four major neuronally active proline-directed kinases, cyclin dependent protein kinase-5, glycogen synthase kinase-3 beta, p42 mitogen-activated protein kinase and stress-activated protein kinase-1b, to phosphorylate APPthr(668) and report here that SAPK1b induces robust phosphorylation of this site both in vitro and in vivo. This finding provides a molecular framework to link cellular stresses with APP metabolism in both normal and disease states.
阿尔茨海默病淀粉样前体蛋白（APP）羧基末端的苏氨酸（668）（Thr(668)）是一个已知的体内磷酸化位点。APP Thr(668)的磷酸化被认为可调节APP的功能和代谢。Thr(668)位于脯氨酸之前，这表明它是脯氨酸定向激酶的磷酸化靶点。我们研究了四种主要的神经元活性脯氨酸定向激酶，即细胞周期蛋白依赖性蛋白激酶5、糖原合酶激酶-3β、p42丝裂原活化蛋白激酶和应激激活蛋白激酶-1b，使APP Thr(668)磷酸化的能力，并在此报告，应激激活蛋白激酶-1b在体外和体内均可诱导该位点的强烈磷酸化。这一发现提供了一个分子框架，将正常和疾病状态下的细胞应激与APP代谢联系起来。
