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Titolo:
p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction
Autore:
Kesavapany, S; Lau, KF; McLoughlin, DM; Brownlees, J; Ackerley, S; Leigh, PN; Shaw, CE; Miller, CCJ;
Indirizzi:
Inst Psychiat, Dept Neurosci, London SE5 8AF, England Inst Psychiat London England SE5 8AF t Neurosci, London SE5 8AF, England Inst Psychiat, Dept Neurol, London SE5 8AF, England Inst Psychiat LondonEngland SE5 8AF ept Neurol, London SE5 8AF, England Inst Psychiat, Old Age Psychiat Sect, London SE5 8AF, England Inst Psychiat London England SE5 8AF chiat Sect, London SE5 8AF, England
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 2, volume: 13, anno: 2001,
pagine: 241 - 247
SICI:
0953-816X(200101)13:2<241:PBAPBA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIN-DEPENDENT KINASE-5; GLYCOGEN-SYNTHASE KINASE-3; DIRECTED PROTEIN-KINASE; CDK5 ACTIVATOR P35; NEUROFILAMENT PROTEINS; ALZHEIMERS-DISEASE; SIGNALING PATHWAY; CDC2-LIKE KINASE; SIDE-ARMS; IN-VITRO;
Keywords:
Alzheimer's disease; human; kinase; neurodegeneration;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Miller, CCJ Inst Psychiat, Dept Neurosci, Denmark Hill, London SE5 8AF, England Inst Psychiat Denmark Hill London England SE5 8AF AF, England
Citazione:
S. Kesavapany et al., "p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction", EUR J NEURO, 13(2), 2001, pp. 241-247

Abstract

The neuronal cyclin-dependent kinase p35/cdk5 comprises a catalytic subunit (cdk5) and an activator subunit (p35). To identify novel p35/cdk5 substrates, we utilized the yeast two-hybrid system to screen for human p35 binding partners. From one such screen, we identified beta -catenin as an interacting protein. Confirmation that p35 binds to beta -catenin was obtained by using glutathione S-transferase (GST)-beta -catenin fusion proteins that interacted with both endogenous and transfected p35, and by showing that beta-catenin was present in p35 immunoprecipitates. p35 and beta -catenin alsodisplayed overlapping subcellular distribution patterns in cells includingneurons. Finally, we demonstrated that p35/cdk5 phosphorylates beta -catenin. beta -catenin also binds to presenilin-1 and altered beta -catenin/presenilin-1 interactions may be mechanistic in Alzheimer's disease (AD). Abnormal p35/cdk5 activity has also been suggested to contribute to AD. We therefore investigated how modulation of p35/cdk5 activity influenced beta -catenin/presenilin-1 interactions. Inhibition of p35/cdk5 with roscovitine did not alter the steady state levels of either beta -catenin or presenilin-1 but reduced the amount of presenilin-1 bound to beta -catenin. Thus, p35/cdk5 binds and phosphorylates beta -catenin and regulates its binding to presenilin-1. The findings reported here therefore provide a novel molecular framework to connect p35/cdk5 with beta -catenin and presenilin-1 in AD.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 00:08:07