Linked Life Data

12556458

Source:http://linkedlifedata.com/resource/pubmed/id/12556458

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2003-4-7
pubmed:abstractText
The final step in A beta generation is the cleavage of the C-terminal 99 amino acid residues of the amyloid precursor protein by gamma-secretase. gamma-Secretase activity is closely linked to the multi-transmembrane-spanning proteins presenilin 1 and presenilin 2. To elucidate whether the cleavage site specificities of gamma-secretase leading to the formation of secreted and intracellular A beta are identical, we made use of point mutations close to the gamma-cleavage site, known to have a dramatic effect on the 42/40 ratio of secreted A beta. We found that the selected point mutations only marginally influenced the 42/40 ratio of intracellular A beta, suggesting differences in the gamma-secretase cleavage site specificity for the generation of secreted and intracellular A beta. The analysis of the subcellular compartments involved in the generation of intracellular A beta revealed that A beta is not generated in the early secretory pathway in the human SH-SY5Y neuroblastoma cell line. In this study we identified late Golgi compartments to be involved in the generation of intracellular A beta. Moreover, we demonstrate that the presence of processed PS1 is not sufficient to obtain gamma-secretase processing of the truncated amyloid precursor protein construct C99, proposing the existence of an additional factor downstream of the endoplasmic reticulum and early Golgi required for the formation of an active gamma-secretase complex.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13077-85
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12556458-Amino Acid Sequence, pubmed-meshheading:12556458-Amino Acid Substitution, pubmed-meshheading:12556458-Amyloid Precursor Protein Secretases, pubmed-meshheading:12556458-Amyloid beta-Peptides, pubmed-meshheading:12556458-Aspartic Acid Endopeptidases, pubmed-meshheading:12556458-Cloning, Molecular, pubmed-meshheading:12556458-Endopeptidases, pubmed-meshheading:12556458-Humans, pubmed-meshheading:12556458-Kinetics, pubmed-meshheading:12556458-Molecular Sequence Data, pubmed-meshheading:12556458-Mutagenesis, Site-Directed, pubmed-meshheading:12556458-Neuroblastoma, pubmed-meshheading:12556458-Point Mutation, pubmed-meshheading:12556458-Recombinant Proteins, pubmed-meshheading:12556458-Substrate Specificity, pubmed-meshheading:12556458-Transfection, pubmed-meshheading:12556458-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
gamma-Secretase cleavage site specificity differs for intracellular and secretory amyloid beta.
pubmed:affiliation
Center for Molecular Biology Heidelberg (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany. h.grimm@mail.zmbh.uni-heidelberg.de
pubmed:publicationType
Journal Article