The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Mutagenesis Identifies New Signals for β-Amyloid Precursor Protein Endocytosis, Turnover, and the Generation of Secreted Fragments, Including Aβ42
Open accessAbstract
It has long been assumed that the C-terminal motif, NPXY, is the internalization signal for beta-amyloid precursor protein (APP) and that the NPXY tyrosine (Tyr743 by APP751 numbering, Tyr682 in APP695) is required for APP endocytosis. To evaluate this tenet and to identify the specific amino acids subserving APP endocytosis, we mutated all tyrosines in the APP cytoplasmic domain and amino acids within the sequence GYENPTY (amino acids 737-743). Stable cell lines expressing these mutations were assessed for APP endocytosis, secretion, and turnover. Normal APP endocytosis was observed for cells expressing Y709A, G737A, and Y743A mutations. However, Y738A, N740A, and P741A or the double mutation of Y738A/P741A significantly impaired APP internalization to a level similar to that observed for cells lacking nearly the entire APP cytoplasmic domain (DeltaC), arguing that the dominant signal for APP endocytosis is the tetrapeptide YENP. Although not an APP internalization signal, Tyr743 regulates rapid APP turnover because half-life increased by 50% with the Y743A mutation alone. Secretion of the APP-derived proteolytic fragment, Abeta, was tightly correlated with APP internalization, such that Abeta secretion was unchanged for cells having normal APP endocytosis but significantly decreased for endocytosis-deficient cell lines. Remarkably, secretion of the Abeta42 isoform was also reduced in parallel with endocytosis from internalization-deficient cell lines, suggesting an important role for APP endocytosis in the secretion of this highly pathogenic Abeta species.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599
Self-citationAmyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921
Self-citationCitron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., & Selkoe, D. J. (1992) · Nature · doi:10.1038/360672a0 · Cited by 1,757
Self-citationIsolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731
Self-citationProduction of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447
Interaction of Tyrosine-Based Sorting Signals with Clathrin-Associated Proteins
Ohno, H., Stewart, J., Fournier, M.-C., Bosshart, H., Rhee, I., Miyatake, S., Saito, T., Gallusser, A., Kirchhausen, T., & Bonifacino, J. S. (1995) · Science · doi:10.1126/science.7569928 · Cited by 969
Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gausepohl, H., & Stanley, K. K. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb03306.x · Cited by 959
Release of Excess Amyloid β Protein from a Mutant Amyloid β Protein Precursor
Cai, X.-D., Golde, T. E., & Younkin, S. G. (1993) · Science · doi:10.1126/science.8424174 · Cited by 913
Haass, C., Koo, E. H., Mellon, A., Hung, A. Y., & Selkoe, D. J. (1992) · Nature · doi:10.1038/357500a0 · Cited by 899
Self-citation
Cited by
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Self-citationAmyloid Precursor Protein Processing and Alzheimer's Disease
O'Brien, R. J., & Wong, P. C. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113613 · Cited by 2,061
Signals for Sorting of Transmembrane Proteins to Endosomes and Lysosomes
Bonifacino, J. S., & Traub, L. M. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161800 · Cited by 2,040
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644
Metadata
- Authors
- Perez, R. G., Soriano, S., Hayes, J. D., Ostaszewski, B., Xia, W., Selkoe, D. J., Chen, X., Stokin, G. B., & Koo, E. H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-07
- Volume
- 274
- Issue
- 27
- Pages
- 18851-18856
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2040732053
- Cited by
- 391
- References
- 54
- FWCI
- 10.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Mutagenesis Identifies New Signals for β-Amyloid Precursor Protein Endocytosis, Turnover, and the Generation of Secreted Fragments, Including Aβ42. https://app.cochat.ai/papers/10.1074/jbc.274.27.18851
- The paper
- Perez, R. G., Soriano, S., Hayes, J. D., Ostaszewski, B., Xia, W., Selkoe, D. J., Chen, X., Stokin, G. B., & Koo, E. H. (1999). Mutagenesis Identifies New Signals for β-Amyloid Precursor Protein Endocytosis, Turnover, and the Generation of Secreted Fragments, Including Aβ42. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.27.18851
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
