rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
3
|
pubmed:dateCreated |
2004-1-12
|
pubmed:abstractText |
The Alzheimer's disease-associated presenilin (PS) 1 is intimately involved in gamma-secretase cleavage of beta-amyloid precursor protein and other proteins. In addition, PS1 plays a role in beta-catenin signaling and in the regulation of apoptosis. Here we demonstrate that phosphorylation of PS1 is regulated by two independent signaling pathways involving protein kinase (PK) A and PKC and that both kinases can directly phosphorylate the large hydrophilic domain of PS1 in vitro and in cultured cells. A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. Moreover, PS1 phosphorylation reduces the progression of apoptosis. Our data indicate that phosphorylation/dephosphorylation at the caspase recognition site provides a mechanism to reversibly regulate properties of PS1 in apoptosis.
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pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jan
|
pubmed:issn |
0021-9258
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
16
|
pubmed:volume |
279
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1585-93
|
pubmed:dateRevised |
2011-11-2
|
pubmed:meshHeading |
pubmed-meshheading:14576165-Amino Acid Sequence,
pubmed-meshheading:14576165-Animals,
pubmed-meshheading:14576165-Apoptosis,
pubmed-meshheading:14576165-COS Cells,
pubmed-meshheading:14576165-Caspases,
pubmed-meshheading:14576165-Cell Line,
pubmed-meshheading:14576165-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:14576165-Glycogen Synthase Kinase 3,
pubmed-meshheading:14576165-Humans,
pubmed-meshheading:14576165-Membrane Proteins,
pubmed-meshheading:14576165-Molecular Sequence Data,
pubmed-meshheading:14576165-Phosphorylation,
pubmed-meshheading:14576165-Presenilin-1,
pubmed-meshheading:14576165-Protein Kinase C,
pubmed-meshheading:14576165-Serine
|
pubmed:year |
2004
|
pubmed:articleTitle |
Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis.
|
pubmed:affiliation |
Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|