ArticleMolecular neurodegeneration2009
The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains.
Article in Molecular neurodegeneration, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 94 citations in OpenAlex.
- Presynaptic accumulation of APP-CTFβ may contribute to synaptic dysfunction in Alzheimer's disease.The EMBO journal · 2026Article
- A Survey of Predicted Protein-Protein Interactions Involving Disordered Regions in Humans.Journal of molecular biology · 2026Article
- Therapeutic Options for Alzheimer's Disease and Aging-Associated Cognitive Decline: State of the Art in the ACH2.0 Paradigm.International journal of molecular sciences · 2026Review
- Alzheimer's Is a Multiform Disease of Sustained Neuronal Integrated Stress Response Driven by the C99 Fragment Generated Independently of AβPP; Proteolytic Production of Aβ Is Suppressed in AD-Affected Neurons: Evolution of a Theory.International journal of molecular sciences · 2025Review
- Article
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations.The Biochemical journal · 2024Review
- Quintessential Synergy: Concurrent Transient Administration of Integrated Stress Response Inhibitors and BACE1 and/or BACE2 Activators as the Optimal Therapeutic Strategy for Alzheimer's Disease.International journal of molecular sciences · 2024Article
- ACH2.0/E, the Consolidated Theory of Conventional and Unconventional Alzheimer's Disease: Origins, Progression, and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- On the Inadequacy of the Current Transgenic Animal Models of Alzheimer's Disease: The Path Forward.International journal of molecular sciences · 2024Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Next Generation Therapeutic Strategy for Treatment and Prevention of Alzheimer's Disease and Aging-Associated Cognitive Decline: Transient, Once-in-a-Lifetime-Only Depletion of Intraneuronal Aβ (International journal of molecular sciences · 2023Article
- Potential Implications of miRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The Amyloid Cascade Hypothesis 2.0 for Alzheimer's Disease and Aging-Associated Cognitive Decline: From Molecular Basis to Effective Therapy.International journal of molecular sciences · 2023Article
- The Involvement of Post-Translational Modifications in Regulating the Development and Progression of Alzheimer's Disease.Molecular neurobiology · 2023Review
- The US9-Derived Protein gPTB9TM Modulates APP Processing Without Targeting Secretase Activities.Molecular neurobiology · 2023Article
- Review
- Vav2 is a novel APP-interacting protein that regulates APP protein level.Scientific reports · 2022Article
- TrkB receptor cleavage by delta-secretase abolishes its phosphorylation of APP, aggravating Alzheimer's disease pathologies.Molecular psychiatry · 2021Article
- APP Binds to the EGFR Ligands HB-EGF and EGF, Acting Synergistically with EGF to Promote ERK Signaling and Neuritogenesis.Molecular neurobiology · 2021Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBrain 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.
resultsHere, 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.
conclusionOur 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.