Cyclin-dependent kinase-5/p35 phosphorylates Presenilin 1 to regulate carboxy-terminal fragment stability

被引:66
作者
Lau, KF
Howlett, DR
Kesavapany, S
Standen, CL
Dingwall, C
McLoughlin, DM
Miller, CCJ
机构
[1] Kings Coll London, Inst Psychiat, Dept Neurosci, London SE5 8AF, England
[2] Kings Coll London, Inst Psychiat, Dept Neurol, London SE5 8AF, England
[3] Kings Coll London, Inst Psychiat, Old Age Psychiat Sect, London SE5 8AF, England
[4] GlaxoSmithKline, Dept Neurol, Harlow CM19 5AW, Essex, England
基金
英国医学研究理事会;
关键词
D O I
10.1006/mcne.2002.1108
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mutations in the Presenilin 1 gene are the cause of the majority of autosomal dominant familial forms of Alzheimer's disease. Presenilin 1 (PS1) is produced as a holoprotein but is then rapidly processed to amino- (N-PS1) and carboxy-terminal (C-PS1) fragments that are incorporated into stable high molecular mass complexes. The mechanisms that control PS1 cleavage and stability are not property understood but sequences within C-PS1 have been shown to regulate both of these properties. Here we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates PS1 on threonine(354) within CPS1 both in vitro and in vivo. Threonine(354) phosphorylation functions to selectively stabilize G-PS1. Our results demonstrate that cdk5/p35 is a regulator of PS1 metabolism.
引用
收藏
页码:13 / 20
页数:8
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