PMID- 16987243
OWN - NLM
STAT- MEDLINE
DCOM- 20061114
LR  - 20220129
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 99
IP  - 1
DP  - 2006 Oct
TI  - Sequential phosphorylation of tau protein by cAMP-dependent protein kinase and 
      SAPK4/p38delta or JNK2 in the presence of heparin generates the AT100 epitope.
PG  - 154-64
AB  - Microtubule-associated protein tau in a hyperphosphorylated state is the major 
      component of the filamentous lesions that define a number of neurodegenerative 
      diseases, including Alzheimer's disease, progressive supranuclear palsy, 
      corticobasal degeneration, Pick's disease, argyrophilic grain disease and 
      frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). 
      Previous work has established that the phosphorylation-dependent anti-tau 
      antibody AT100 is a specific marker for filamentous tau in adult human brain. 
      Here we have identified protein kinases that generate the AT100 epitope in vitro 
      and have used them, in conjunction with site-directed mutagenesis of tau, to map 
      the epitope. We show that the sequential phosphorylation of recombinant tau by 
      cAMP-dependent protein kinase (PKA) and the stress-activated protein kinases 
      SAPK4/p38delta or JNK2 generated the AT100 epitope and that this required 
      phosphorylation of T212, S214 and T217. Tau protein from newborn, but not adult, 
      mouse brain was weakly labelled by AT100. Phosphorylation by PKA and 
      SAPK4/p38delta abolished the ability of tau to promote microtubule assembly, but 
      failed to influence significantly the heparin-induced assembly of tau into 
      filaments.
FAU - Yoshida, Hirotaka
AU  - Yoshida H
AD  - Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. 
      hiro@mrc-lmb.cam.ac.uk
FAU - Goedert, Michel
AU  - Goedert M
LA  - eng
GR  - MC_U105184291/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Peptide Fragments)
RN  - 0 (tau Proteins)
RN  - 9005-49-6 (Heparin)
RN  - EC 2.7.1.- (Mitogen-Activated Protein Kinase 13)
RN  - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Enzyme Activation
MH  - Heparin/*pharmacology
MH  - Kinetics
MH  - Mice
MH  - Microtubules/physiology
MH  - Mitogen-Activated Protein Kinase 13/*metabolism
MH  - Mitogen-Activated Protein Kinase 9/*metabolism
MH  - Peptide Fragments/chemistry/metabolism
MH  - Phosphorylation
MH  - tau Proteins/*metabolism
EDAT- 2006/09/22 09:00
MHDA- 2006/11/15 09:00
CRDT- 2006/09/22 09:00
PHST- 2006/09/22 09:00 [pubmed]
PHST- 2006/11/15 09:00 [medline]
PHST- 2006/09/22 09:00 [entrez]
AID - JNC4052 [pii]
AID - 10.1111/j.1471-4159.2006.04052.x [doi]
PST - ppublish
SO  - J Neurochem. 2006 Oct;99(1):154-64. doi: 10.1111/j.1471-4159.2006.04052.x.