PMID- 1376245
OWN - NLM
STAT- MEDLINE
DCOM- 19920714
LR  - 20220511
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 11
IP  - 6
DP  - 1992 Jun
TI  - Mitogen activated protein (MAP) kinase transforms tau protein into an 
      Alzheimer-like state.
PG  - 2131-8
AB  - The microtubule-associated protein tau is a major component of the paired helical 
      filaments (PHFs) observed in Alzheimer's disease brains. The pathological tau is 
      distinguished from normal tau by its state of phosphorylation, higher apparent 
      M(r) and reaction with certain antibodies. However, the protein kinase(s) have 
      not been characterized so far. Here we describe a protein kinase from brain which 
      specifically induces the Alzheimer-like state in tau protein. The 42 kDa protein 
      belongs to the family of mitogen activated protein kinases (MAPKs) and is 
      activated by tyrosine phosphorylation. It is capable of phosphorylating Ser-Pro 
      and Thr-Pro motifs in tau protein (approximately 14-16 P1 per tau molecule). By 
      contrast, other proline directed Ser/Thr kinases such as p34(cdc2) combined with 
      cyclin A or B have only minor effects on tau phosphorylation. We propose that MAP 
      kinase is abnormally active in Alzheimer brain tissue, or that the corresponding 
      phosphatases are abnormally passive, due to a breakdown of the normal regulatory 
      mechanisms.
FAU - Drewes, G
AU  - Drewes G
AD  - Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
FAU - Lichtenberg-Kraag, B
AU  - Lichtenberg-Kraag B
FAU - Doring, F
AU  - Doring F
FAU - Mandelkow, E M
AU  - Mandelkow EM
FAU - Biernat, J
AU  - Biernat J
FAU - Goris, J
AU  - Goris J
FAU - Doree, M
AU  - Doree M
FAU - Mandelkow, E
AU  - Mandelkow E
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Recombinant Proteins)
RN  - 0 (tau Proteins)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Animals
MH  - Brain/*enzymology
MH  - Calcium-Calmodulin-Dependent Protein Kinases
MH  - Cattle
MH  - Chromatography, Ion Exchange
MH  - Cloning, Molecular
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme Activation
MH  - Humans
MH  - Molecular Weight
MH  - Phosphorylation
MH  - Phosphotyrosine
MH  - Protein Kinases/genetics/isolation & purification/*metabolism
MH  - Recombinant Proteins/isolation & purification/metabolism
MH  - Reference Values
MH  - Substrate Specificity
MH  - Swine
MH  - Tyrosine/analogs & derivatives/analysis
MH  - tau Proteins/genetics/*metabolism
PMC - PMC556680
EDAT- 1992/06/01 00:00
MHDA- 1992/06/01 00:01
PMCR- 1993/06/01
CRDT- 1992/06/01 00:00
PHST- 1992/06/01 00:00 [pubmed]
PHST- 1992/06/01 00:01 [medline]
PHST- 1992/06/01 00:00 [entrez]
PHST- 1993/06/01 00:00 [pmc-release]
AID - 10.1002/j.1460-2075.1992.tb05272.x [doi]
PST - ppublish
SO  - EMBO J. 1992 Jun;11(6):2131-8. doi: 10.1002/j.1460-2075.1992.tb05272.x.