2001
DOI: 10.1042/bss0670073
|View full text |Cite
|
Sign up to set email alerts
|

Sites of phosphorylation in tau and factors affecting their regulation

Abstract: The microtubule-associated protein, tau, is the principal component of paired helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated and a total of 25 sites of phosphorylation have so far been identified. Many of these sites are serine or threonine residues that are immediately followed in the sequence by proline residues, and hence are candidate phosphorylation sites for proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3), extracellular signal-related kinase-1 and… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1

Citation Types

1
33
0
1

Year Published

2006
2006
2015
2015

Publication Types

Select...
8
1

Relationship

2
7

Authors

Journals

citations
Cited by 89 publications
(36 citation statements)
references
References 12 publications
1
33
0
1
Order By: Relevance
“…Tau hyperphosphorylation at Thr-212, Ser-202, Ser-396, and Ser-404 is found in paired helical filaments in AD brains (42,45). Reduction in A␤ 1-42 levels leads to GSK-3␤ inactivation and prevents Tau phosphorylation in vivo and in vitro (21,23).…”
Section: Discussionmentioning
confidence: 99%
“…Tau hyperphosphorylation at Thr-212, Ser-202, Ser-396, and Ser-404 is found in paired helical filaments in AD brains (42,45). Reduction in A␤ 1-42 levels leads to GSK-3␤ inactivation and prevents Tau phosphorylation in vivo and in vitro (21,23).…”
Section: Discussionmentioning
confidence: 99%
“…These two phosphomimics, both human 2N4R tau, simulate permanent phosphorylation at 18 and 27 phosphorylation sites, respectively, by mutation of serine or threonine residues to glutamate, which mimics the presence of a phosphate group (28). All the mutated sites are known to be present in PHF tau, and the majority are phosphorylated by GSK-3 in vitro (2,3,41). E18tau and E27tau mimic functional aspects of GSK-3-phosphorylated tau protein, including a reduced ability to promote microtubule assembly (28,42,43).…”
Section: Phosphomimic Tau Mutants Are Transported Faster Than Wild-tymentioning
confidence: 99%
“…Tau hyperphosphorylation arises as a result of aberrant protein kinase and/or phosphatase activity and an increasing number of protein kinases have been shown to phosphorylate tau at epitopes of relevance to AD (Hanger et al 1992(Hanger et al , 2007Baumann et al 1993;Goedert et al 1997;Reynolds et al 1997;Anderton et al 2001;Guise et al 2001;Derkinderen et al 2005). In tau transgenic mice, specific and broad-range protein kinase inhibitors can lower abnormal tau phosphorylation and aggregation, and significantly reduce both neuronal degeneration (Noble et al 2005;Le Corre et al 2006) and behavioral deficits (Le Corre et al 2006).…”
mentioning
confidence: 99%