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Tamayev R, Zhou D, D'Adamio L. The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains. Mol Neurodegener. 2009;4:28doi: 10.1186/1750-1326-4-28.
Tamayev, R., Zhou, D., & D'Adamio, L. (2009). The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains. Molecular neurodegeneration, 428. https://doi.org/10.1186/1750-1326-4-28
Tamayev, Robert, et al. "The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains." Molecular neurodegeneration vol. 4 (2009): 28. doi: https://doi.org/10.1186/1750-1326-4-28
Tamayev R, Zhou D, D'Adamio L. The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains. Mol Neurodegener. 2009 Jul 14;4:28. doi: 10.1186/1750-1326-4-28. PMID: 19602287; PMCID: PMC2723102.
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Mol Neurodegener. 2009 Jul 14;4:28. doi: 10.1186/1750-1326-4-28.

The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains.

Molecular neurodegeneration

Robert Tamayev, Dawang Zhou, Luciano D'Adamio

Affiliations

  1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA. [email protected].

PMID: 19602287 PMCID: PMC2723102 DOI: 10.1186/1750-1326-4-28

Abstract

BACKGROUND: Brain tissue from patients with Alzheimer's disease has shown an increase of phosphorylation of Tyr-682, located on the conserved Y682ENPTY motif, and Thr-668 residues, both in the intracellular domain (AID) of amyloid beta precursor protein (APP), although the role of these two residues is not yet known.

RESULTS: Here, we report that the phosphorylation status of Tyr-682, and in some cases Thr-668, shapes the APP interactome. It creates a docking site for SH2-domain containing proteins, such as ShcA, ShcB, ShcC, Grb7, Grb2, as well as adapter proteins, such as Crk and Nck, that regulate important biological processes, cytosolic tyrosine kinases, such as Abl, Lyn and Src, which regulate signal transduction pathways, and enzymes that control phosphatidylinositols levels and signaling, such as PLC-gamma. At the same time, it either reduces (like for JIP1, NUMB, NUMBL and ARH) or abolishes (like for Fe65, Fe65L1 and Fe65L2) binding of other APP interactors. Phosphorylation of Thr-668, unlike Tyr-682, does not seem to affect APP's ability to interact with the various proteins, with Pin1 and X11 being the exclusions. We also found that there are some differences between the interactions to AID and to ALID1 and ALID2, its two homologues.

CONCLUSION: Our data indicates that APP can regulate diverse cellular processes and that, vice versa, a network of signaling events can impact APP processing. Our results also suggest that phosphorylation of the APP Intracellular Domain will dramatically shape the APP interactome and, consequently, will regulate APP processing, APP transport and APP/AID-mediated functions.

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