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c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice.

Authors: Cancino, GI  Perez de Arce, K  Castro, PU  Toledo, EM  Von Bernhardi, R  Alvarez, AR 
Citation: Cancino GI, etal., Neurobiol Aging. 2011 Jul;32(7):1249-61. doi: 10.1016/j.neurobiolaging.2009.07.007. Epub 2009 Aug 22.
Pubmed: (View Article at PubMed) PMID:19700222
DOI: Full-text: DOI:10.1016/j.neurobiolaging.2009.07.007

The c-Abl tyrosine kinase is an important link in signal transduction pathways that promote cytoskeletal rearrangement and apoptotic signalling. We have previously shown that amyloid-beta-peptide (Abeta) activates c-Abl. Herein we show that c-Abl participates in Abeta-induced tau phosphorylation through Cdk5 activation. We found that intraperitoneal administration of STI571, a specific inhibitor for c-Abl kinase, decreased tau phosphorylation in the APPswe/PSEN1DeltaE9 transgenic mouse brain. In addition, when neurons were treated with Abeta we observed: (i) an increase in active c-Abl and tau phosphorylation, (ii) the prevention of tau phosphorylation by STI571 and (iii) the inhibition of c-Abl expression by shRNA, as well as the expression of a c-Abl kinase death mutant, decreased AT8 and PHF1 signals. Furthermore, the increase of c-Abl was associated with Tyr15 phosphorylation of Cdk5 and its association with c-Abl. Brains from APPswe/PSEN1DeltaE9 mice showed higher levels of c-Abl and phospho-Cdk5 than wild-type mice. Moreover, STI571 treatment decreased the phospho-Cdk5 levels. Together, the evidence suggests that activation of c-Abl by Abeta promotes tau phosphorylation through Tyr15 phosphorylation-mediated Cdk5 activation.


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CRRD Object Information
CRRD ID: 8693570
Created: 2014-07-16
Species: All species
Last Modified: 2014-07-16
Status: ACTIVE


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