PMID- 7566349
OWN - NLM
STAT- MEDLINE
DCOM- 19951107
LR  - 20190909
IS  - 0197-4580 (Print)
IS  - 0197-4580 (Linking)
VI  - 16
IP  - 3
DP  - 1995 May-Jun
TI  - Secreted beta-APP stimulates MAP kinase and phosphorylation of tau in neurons.
PG  - 403-7; discussion 407-8
AB  - We have previously demonstrated that the secreted form of the beta-amyloid 
      precursor protein (beta-APP) activates mitogen-activated protein (MAP) kinases in 
      PC-12 pheochromocytoma cells. beta-APP as well as other treatments that activate 
      MAP kinase also enhance phosphorylation of the microtubule-associated protein tau 
      in these cells. In this study, we extended this analysis to neurons. Using 
      dissociated cultures of cortical neurons, we found that exposure to beta-APP 
      activated MAP kinase 4 and 7 days but not 1 day after plating. Phosphorylation of 
      tau in neurons was measured by immunoreactivity with the AT8 antibody, which 
      recognizes a phosphorylated epitope present in tau from paired helical filaments. 
      We found that activation of MAP kinase in neurons was associated with increased 
      amounts of AT8-reactive tau. These results support a role for MAP kinase in 
      transducing the biological effects of secreted beta-APP on neurons and suggest 
      possible mechanisms by which beta-APP might be involved in the pathogenesis of 
      Alzheimer's disease.
FAU - Greenberg, S M
AU  - Greenberg SM
AD  - Department of Neurology, Harvard Medical School, Brigham and Women's Hospital, 
      Boston, MA 02115, USA.
FAU - Kosik, K S
AU  - Kosik KS
LA  - eng
GR  - AG06601/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (tau Proteins)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Amyloid beta-Protein Precursor/metabolism/*physiology
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cells, Cultured
MH  - Enzyme Activation/physiology
MH  - Neurons/enzymology/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - tau Proteins/*metabolism
EDAT- 1995/05/01 00:00
MHDA- 1995/05/01 00:01
CRDT- 1995/05/01 00:00
PHST- 1995/05/01 00:00 [pubmed]
PHST- 1995/05/01 00:01 [medline]
PHST- 1995/05/01 00:00 [entrez]
AID - 019745809400172W [pii]
AID - 10.1016/0197-4580(94)00172-w [doi]
PST - ppublish
SO  - Neurobiol Aging. 1995 May-Jun;16(3):403-7; discussion 407-8. doi: 
      10.1016/0197-4580(94)00172-w.