RGD Reference Report - Phosphorylation of FTDP-17 mutant tau by cyclin-dependent kinase 5 complexed with p35, p25, or p39. - Rat Genome Database

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Phosphorylation of FTDP-17 mutant tau by cyclin-dependent kinase 5 complexed with p35, p25, or p39.

Authors: Sakaue, F  Saito, T  Sato, Y  Asada, A  Ishiguro, K  Hasegawa, M  Hisanaga, S 
Citation: Sakaue F, etal., J Biol Chem. 2005 Sep 9;280(36):31522-9. Epub 2005 Jul 1.
RGD ID: 8553752
Pubmed: PMID:15994305   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M504792200   (Journal Full-text)

One of the major pathological hallmarks of Alzheimer disease is neurofibrillary tangles. Neurofibrillary tangles are bundles of paired helical filaments composed of hyperphosphorylated tau. Cyclin-dependent kinase 5 (Cdk5) is one of the tau protein kinases that increase paired helical filament epitopes in tau by phosphorylation. Recently, various mutations of tau have been identified in frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Here, we investigated the phosphorylation of FTDP-17 mutant tau proteins, K257T, P301L, P301S, and R406W, by Cdk5 complexed with p35, p25, or p39 in vitro and in cultured cells. The extent of phosphorylation by all Cdk5 species was slightly lower in mutant tau than in wild-type tau. Major phosphorylation sites, including Ser202, Ser235, and Ser404, were the same among the wild-type, K257T, P301L, and P301S tau proteins phosphorylated by any Cdk5. On the other hand, R406W tau was less phosphorylated at Ser404 than were the other variants. This was not due to the simple replacement of amino acid Arg406 with Trp close to the phosphorylation site, because Ser404 in a R406W peptide was equally phosphorylated in a wild-type peptide. The decreased phosphorylation of mutant tau by Cdk5s was canceled when tau protein bound to microtubules was phosphorylated. These results indicate that FTDP-17 mutations do not affect the phosphorylatability of tau by Cdk5 complexed with p35, p25, or p39 and may explain part of the discrepancy reported previously between in vivo and in vitro phosphorylation of FTDP-17 tau mutants.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cdk5r1Ratprotein serine/threonine kinase activator activity enablesIDA PMID:15994305UniProt 
Cdk5Ratprotein serine/threonine kinase activity enablesIDA PMID:15994305UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Cdk5  (cyclin-dependent kinase 5)
Cdk5r1  (cyclin-dependent kinase 5 regulatory subunit 1)


Additional Information