PMID- 7559474
OWN - NLM
STAT- MEDLINE
DCOM- 19951114
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 40
DP  - 1995 Oct 6
TI  - Regulated formation of Golgi secretory vesicles containing Alzheimer beta-amyloid 
      precursor protein.
PG  - 23243-5
AB  - Phorbol esters, activators of protein kinase C (PKC), regulate the relative 
      utilization of alternative processing pathways for the Alzheimer beta-amyloid 
      precursor protein (beta-APP) in intact cells, increasing the production of 
      nonamyloidogenic soluble beta-APP (s beta-APP) and decreasing that of neurotoxic 
      beta-amyloid (A beta) peptide. The molecular and cellular bases of PKC-regulated 
      beta-APP cleavage are poorly understood. Here we demonstrate in a reconstituted 
      cell-free system that activation of endogenous PKC increases formation from the 
      trans-Golgi network of secretory vesicles containing beta-APP and that this 
      effect can be mimicked by purified PKC. The results demonstrate directly that PKC 
      is involved in regulation of secretory vesicle formation and provide a mechanism 
      by which PKC may reduce the formation of the A beta peptide characteristic of 
      Alzheimer disease.
FAU - Xu, H
AU  - Xu H
AD  - Department of Neurology and Neuroscience, Cornell University Medical College, New 
      York, New York 10021, USA.
FAU - Greengard, P
AU  - Greengard P
FAU - Gandy, S
AU  - Gandy S
LA  - eng
GR  - AG09464/AG/NIA NIH HHS/United States
GR  - AG10491/AG/NIA NIH HHS/United States
GR  - AG11508/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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Aluminum Compounds)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 37558-16-0 (Phorbol 12,13-Dibutyrate)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - Q80VPU408O (Fluorides)
RN  - Z77H3IKW94 (aluminum fluoride)
SB  - IM
MH  - Aluminum Compounds/pharmacology
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Biological Transport, Active
MH  - Cell-Free System
MH  - Enzyme Activation/drug effects
MH  - Fluorides/pharmacology
MH  - Golgi Apparatus/drug effects/*metabolism
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
MH  - Humans
MH  - PC12 Cells
MH  - Phorbol 12,13-Dibutyrate/pharmacology
MH  - Protein Kinase C/metabolism
MH  - Rats
EDAT- 1995/10/06 00:00
MHDA- 1995/10/06 00:01
CRDT- 1995/10/06 00:00
PHST- 1995/10/06 00:00 [pubmed]
PHST- 1995/10/06 00:01 [medline]
PHST- 1995/10/06 00:00 [entrez]
AID - S0021-9258(18)89901-X [pii]
AID - 10.1074/jbc.270.40.23243 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Oct 6;270(40):23243-5. doi: 10.1074/jbc.270.40.23243.