PMID- 9844014
OWN - NLM
STAT- MEDLINE
DCOM- 19990114
LR  - 20230331
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 95
IP  - 25
DP  - 1998 Dec 8
TI  - Specific intercellular binding of the beta-amyloid precursor protein to the 
      presenilins induces intercellular signaling: its significance for Alzheimer's 
      disease.
PG  - 15055-60
AB  - Genetic evidence has implicated three proteins, the beta-amyloid precursor 
      protein (beta-APP) and the two homologous presenilins (PS-1 and PS-2), in the 
      etiology of Alzheimer's disease (AD). How these three proteins jointly contribute 
      to AD, however, is not clear. Nor is any of their normal physiological functions 
      known. Herein, we demonstrate, confirming a prediction made earlier, that 
      beta-APP and either PS-1 or PS-2 act as a specific membrane-bound ligand binding 
      intercellularly with either of its two membrane receptors. This results in a 
      cell-cell adhesion, after which rapid transient increases in protein tyrosine 
      kinase activity and protein tyrosine phosphorylation occur coordinately inside 
      one or both of the two adherent cells. The spectrum of proteins modified by 
      tyrosine phosphorylation differs depending on whether PS-1 or PS-2 is involved in 
      the specific intercellular binding to beta-APP, which implies that PS-1 and PS-2 
      have distinct, rather than redundant, functions in normal physiology. The 
      relevance of this intercellular interaction and signaling process to AD is 
      discussed.
FAU - Dewji, N N
AU  - Dewji NN
AD  - Department of Medicine, University of California at San Diego, 9500 Gilman Drive, 
      La Jolla, CA 92093-0322, USA. dewji@biomail.ucsd.edu
FAU - Singer, S J
AU  - Singer SJ
LA  - eng
GR  - 2RO1-NS27850/NS/NINDS NIH HHS/United States
PT  - Journal Article
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  - 0 (Membrane Proteins)
SB  - IM
MH  - Alzheimer Disease/metabolism/*physiopathology
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Cell Line
MH  - Humans
MH  - Membrane Proteins/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Signal Transduction/*physiology
PMC - PMC24574
EDAT- 1998/12/09 00:00
MHDA- 1998/12/09 00:01
PMCR- 1999/06/08
CRDT- 1998/12/09 00:00
PHST- 1998/12/09 00:00 [pubmed]
PHST- 1998/12/09 00:01 [medline]
PHST- 1998/12/09 00:00 [entrez]
PHST- 1999/06/08 00:00 [pmc-release]
AID - 3994 [pii]
AID - 10.1073/pnas.95.25.15055 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15055-60. doi: 
      10.1073/pnas.95.25.15055.