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- W2157750054 startingPage "1299" @default.
- W2157750054 abstract "J. Neurochem. (2010) 115, 1299–1308. Abstract In recent decades, the study of the amyloid precursor protein (APP) and of its proteolytic products carboxy terminal fragment (CTF), APP intracellular C‐terminal domain (AICD) and amyloid beta has been mostly focussed on the role of APP as a producer of the toxic amyloid beta peptide. Here, we reconsider the role of APP suggesting, in a provocative way, the protein as a central player in a putative signalling pathway. We highlight the presence in the cytosolic tail of APP of the YENPTY motif which is typical of tyrosine kinase receptors, the phosphorylation of the tyrosine, serine and threonine residues, the kinases involved and the interaction with intracellular adaptor proteins. In particular, we examine the interaction with Shc and Grb2 regulators, which through the activation of Ras proteins elicit downstream signalling events such as the MAPK pathway. The review also addresses the interaction of APP, CTFs and AICD with other adaptor proteins and in particular with Fe65 for nuclear transcriptional activity and the importance of phosphorylation for sorting the secretases involved in the amyloidogenic or non‐amyloidogenic pathways. We provide a novel perspective on Alzheimer’s disease pathogenesis, focussing on the perturbation of the physiological activities of APP‐CTFs and AICD as an alternative perspective from that which normally focuses on the accumulation of neurotoxic proteolytic fragments." @default.
- W2157750054 created "2016-06-24" @default.
- W2157750054 creator A5000672475 @default.
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- W2157750054 creator A5073715352 @default.
- W2157750054 date "2010-11-04" @default.
- W2157750054 modified "2023-10-16" @default.
- W2157750054 title "Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: signal transduction and/or transcriptional role - relevance for Alzheimer pathology" @default.
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- W2157750054 doi "https://doi.org/10.1111/j.1471-4159.2010.07044.x" @default.
- W2157750054 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21039524" @default.
- W2157750054 hasPublicationYear "2010" @default.
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