In contrast, the DAPK1 fragments from 1 to 1423, from 637 to 1423 and from 848 to 1423 efficiently bound to APP, suggesting that the death domain (1271–1423, DD) is likely bound to APP (Fig. 4F).
DAPK1, but not its kinase deficient mutant (K42A), significantly increased human Aβ secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased Aβ secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Aβ.
Furthermore, DAPK1-induced APP phosphorylation was suppressed when DAPK1 ΔDD was introduced (Fig. 4G), indicating that DAPK1 regulates Aβ secretion through APP Thr668 phosphorylation.
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.