PMID- 27641626
OWN - NLM
STAT- MEDLINE
DCOM- 20180604
LR  - 20191210
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Sep 19
TI  - Quantitative and combinatory determination of in situ phosphorylation of tau and 
      its FTDP-17 mutants.
PG  - 33479
LID - 10.1038/srep33479 [doi]
LID - 33479
AB  - Tau is hyperphosphorylated in the brains of patients with tauopathies, such as 
      Alzheimer's disease and frontotemporal dementia and parkinsonism linked to 
      chromosome 17 (FTDP-17). However, neither the mechanism of hyperphosphorylation 
      nor its contribution to pathogenesis is known. We applied Phos-tag SDS-PAGE, a 
      phosphoaffinity electrophoresis, to the analysis of tau phosphorylation in vitro 
      by Cdk5, in cultured cells and in mouse brain. Here, we found that Cdk5-p25 
      phosphorylated tau in vitro at Ser404, Ser235, Thr205 and Ser202 in this order. 
      In contrast in cultured cells, Ser404 was preferentially phosphorylated by 
      Cdk5-p35, whereas Thr205 was not phosphorylated. Ser202 and Ser235 were 
      phosphorylated by endogenous kinases. Tau exhibited ~12 phosphorylation isotypes 
      in COS-7 cells with different combinations of phosphorylation at Thr181, Ser202, 
      Thr231, Ser235 and Ser404. These phosphorylation sites were similar to tau 
      phosphorylated in mouse brains. FTDP-17 tau with a mutation in the C-terminal 
      region had different banding patterns, indicating a different phosphorylation 
      pattern. In particular, it was clear that the R406W mutation causes loss of 
      Ser404 phosphorylation. These results demonstrate the usefulness of the Phos-tag 
      technique in the quantitative analysis of site-specific in vivo phosphorylation 
      of tau and provide detailed information on in situ combinatory phosphorylation of 
      tau.
FAU - Kimura, Taeko
AU  - Kimura T
AD  - Laboratory of Molecular Neuroscience, Department of Biological Sciences, Tokyo 
      Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
FAU - Hosokawa, Tomohisa
AU  - Hosokawa T
AD  - Laboratory of Molecular Neuroscience, Department of Biological Sciences, Tokyo 
      Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
FAU - Taoka, Masato
AU  - Taoka M
AD  - Department of Chemistry, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, 
      Japan.
FAU - Tsutsumi, Koji
AU  - Tsutsumi K
AD  - Laboratory of Molecular Neuroscience, Department of Biological Sciences, Tokyo 
      Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
FAU - Ando, Kanae
AU  - Ando K
AD  - Laboratory of Molecular Neuroscience, Department of Biological Sciences, Tokyo 
      Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
FAU - Ishiguro, Koichi
AU  - Ishiguro K
AD  - Juntendo University, Tokyo, 113-0033, Japan.
FAU - Hosokawa, Masato
AU  - Hosokawa M
AD  - Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
FAU - Hasegawa, Masato
AU  - Hasegawa M
AD  - Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
FAU - Hisanaga, Shin-Ichi
AU  - Hisanaga S
AD  - Laboratory of Molecular Neuroscience, Department of Biological Sciences, Tokyo 
      Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160919
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Mutant Proteins)
RN  - 0 (tau Proteins)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (CDK5 protein, human)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/genetics
MH  - Amino Acid Sequence
MH  - Animals
MH  - Brain/metabolism/pathology
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Cyclin-Dependent Kinase 5/metabolism
MH  - Frontotemporal Dementia/*genetics/*metabolism
MH  - Mice
MH  - Models, Biological
MH  - Mutant Proteins/chemistry/metabolism
MH  - Mutation/*genetics
MH  - Phosphorylation
MH  - tau Proteins/chemistry/*metabolism
PMC - PMC5027580
EDAT- 2016/09/20 06:00
MHDA- 2018/06/05 06:00
PMCR- 2016/09/19
CRDT- 2016/09/20 06:00
PHST- 2016/03/11 00:00 [received]
PHST- 2016/08/24 00:00 [accepted]
PHST- 2016/09/20 06:00 [entrez]
PHST- 2016/09/20 06:00 [pubmed]
PHST- 2018/06/05 06:00 [medline]
PHST- 2016/09/19 00:00 [pmc-release]
AID - srep33479 [pii]
AID - 10.1038/srep33479 [doi]
PST - epublish
SO  - Sci Rep. 2016 Sep 19;6:33479. doi: 10.1038/srep33479.