PMID- 8041753
OWN - NLM
STAT- MEDLINE
DCOM- 19940822
LR  - 20211203
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 91
IP  - 15
DP  - 1994 Jul 19
TI  - Secreted beta-amyloid precursor protein stimulates mitogen-activated protein 
      kinase and enhances tau phosphorylation.
PG  - 7104-8
AB  - Biological effects related to cell growth, as well as a role in the pathogenesis 
      of Alzheimer disease, have been ascribed to the beta-amyloid precursor protein 
      (beta-APP). Little is known, however, about the intracellular cascades that 
      mediate these effects. We report that the secreted form of beta-APP potently 
      stimulates mitogen-activated protein kinases (MAPKs). Brief exposure of PC-12 
      pheochromocytoma cells to beta-APP secreted by transfected Chinese hamster ovary 
      cells stimulated the 43-kDa form of MAPK by > 10-fold. Induction of a dominant 
      inhibitory form of ras in a PC12-derived cell line prevented the stimulation of 
      MAPK by secreted beta-APP, demonstrating the dependence of the effect upon 
      p21ras. Because the microtubule-associated protein tau is hyperphosphorylated in 
      Alzheimer disease, we sought and found a 2-fold enhancement in tau 
      phosphorylation associated with the beta-APP-induced MAPK stimulation. In the ras 
      dominant inhibitory cell line, beta-APP failed to enhance phosphorylation of tau. 
      The data presented here provide a link between secreted beta-APP and the 
      phosphorylation state of tau.
FAU - Greenberg, S M
AU  - Greenberg SM
AD  - Department of Neurology, Harvard Medical School, Boston, MA.
FAU - Koo, E H
AU  - Koo EH
FAU - Selkoe, D J
AU  - Selkoe DJ
FAU - Qiu, W Q
AU  - Qiu WQ
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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - CHO Cells
MH  - Cricetinae
MH  - Cricetulus
MH  - Enzyme Activation
MH  - Mitogen-Activated Protein Kinase 1
MH  - PC12 Cells
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proto-Oncogene Proteins p21(ras)/metabolism
PMC - PMC44347
EDAT- 1994/07/19 00:00
MHDA- 1994/07/19 00:01
PMCR- 1995/01/19
CRDT- 1994/07/19 00:00
PHST- 1994/07/19 00:00 [pubmed]
PHST- 1994/07/19 00:01 [medline]
PHST- 1994/07/19 00:00 [entrez]
PHST- 1995/01/19 00:00 [pmc-release]
AID - 10.1073/pnas.91.15.7104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7104-8. doi: 
      10.1073/pnas.91.15.7104.