GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:9689133

From GONUTS
Jump to: navigation, search
Citation

Takashima, A, Murayama, M, Murayama, O, Kohno, T, Honda, T, Yasutake, K, Nihonmatsu, N, Mercken, M, Yamaguchi, H, Sugihara, S and Wolozin, B (1998) Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Proc. Natl. Acad. Sci. U.S.A. 95:9637-41

Abstract

Families bearing mutations in the presenilin 1 (PS1) gene develop Alzheimer's disease. Previous studies have shown that the Alzheimer-associated mutations in PS1 increase production of amyloid beta protein (Abeta1-42). We now show that PS1 also regulates phosphorylation of the microtubule-associated protein tau. PS1 directly binds tau and a tau kinase, glycogen synthase kinase 3beta (GSK-3beta). Deletion studies show that both tau and GSK-3beta bind to the same region of PS1, residues 250-298, whereas the binding domain on tau is the microtubule-binding repeat region. The ability of PS1 to bring tau and GSK-3beta into close proximity suggests that PS1 may regulate the interaction of tau with GSK-3beta. Mutations in PS1 that cause Alzheimer's disease increase the ability of PS1 to bind GSK-3beta and, correspondingly, increase its tau-directed kinase activity. We propose that the increased association of GSK-3beta with mutant PS1 leads to increased phosphorylation of tau.

Links

PubMed PMC21391

Keywords

Adult; Aged; Aged, 80 and over; Brain/enzymology; Brain/metabolism; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Chromatography, Affinity; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; Humans; Infant, Newborn; Membrane Proteins/isolation & purification; Membrane Proteins/metabolism; Middle Aged; Precipitin Tests; Presenilin-1; Substrate Specificity; tau Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TAU

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49768

F

Seeded From UniProt

complete

HUMAN:PSN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P10636

F

Seeded From UniProt

complete

HUMAN:PSN1

involved_in

GO:0042325: regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.