Glycogen Synthase Kinase 3β Phosphorylates Tau at Both Primed and Unprimed Sites
Open accessAbstract
Glycogen synthase kinase 3beta (GSK3beta) phosphorylates substrates, including the microtubule-associated protein tau, at both primed and unprimed epitopes. GSK3beta phosphorylation of tau negatively regulates tau-microtubule interactions; however the differential effects of phosphorylation at primed and unprimed epitopes on tau is unknown. To examine the phosphorylation of tau at primed and unprimed epitopes and how this impacts tau function, the R96A mutant of GSK3beta was used, a mutation that prevents phosphorylation of substrates at primed sites. Both GSK3beta and GSK3beta-R96A phosphorylated tau efficiently in situ. However, expression of GSK3beta-R96A resulted in significantly less phosphorylation of tau at primed sites compared with GSK3beta. Conversely, GSK3beta-R96A phosphorylated unprimed tau sites to a significantly greater extent than GSK3beta. Prephosphorylating tau with cdk5/p25 impaired the ability of GSK3beta-R96A to phosphorylate tau, whereas GSK3beta-R96A phosphorylated recombinant tau to a significantly greater extent than GSK3beta. Moreover, the amount of tau associated with microtubules was reduced by overexpression of GSK3beta but only when tau was phosphorylated at primed sites, as phosphorylation of tau by GSK3beta-R96A did not negatively regulate the association of tau with microtubules. These results demonstrate that GSK3beta-mediated phosphorylation of tau at primed sites plays a more significant role in regulating the interaction of tau with micro…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Phosphorylation of tau on Ser(P)-214 and Thr(P)-231 reduces the ability of tau to bind microtubules.
“Phosphorylation of tau on Ser(P)-214 and Thr(P)-231 is also reported to reduce the ability of tau to bind microtubules (12).”
From An Unbiased Approach to Identifying Tau Kinases That Phosphorylate Tau at Sites Associated with Alzheimer Disease (2013) · cites this paper as [12]
Cites
Cleveland, D. W., Hwo, S.-Y., & Kirschner, M. W. (1977) · Journal of Molecular Biology · doi:10.1016/0022-2836(77)90213-3 · Cited by 915 · see citing works
Phosphorylation affects the ability of tau protein to promote microtubule assembly.
Lindwall, G., & Cole, R. D. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42989-9 · Cited by 901 · see citing works
Monoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
Otvos, L., Feiner, L., Lang, E., Szendrei, G. I., Goedert, M., & Lee, V. M. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390607 · Cited by 488 · see citing works
Goedert, M., Jakes, R., Crowther, R. A., Cohen, P., Vanmechelen, E., Vandermeeren, M., & Cras, P. (1994) · Biochemical Journal · doi:10.1042/bj3010871 · Cited by 375 · see citing works
Maas, T., Eidenmüller, J., & Brandt, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000389200 · Cited by 226 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells
Israel, M. A., Yuan, S. H., Bardy, C., Reyna, S. M., Mu, Y., Herrera, C., Hefferan, M. P., Van Gorp, S., Nazor, K. L., Boscolo, F. S., et al. (2012) · Nature · doi:10.1038/nature10821 · Cited by 1,253 · see citing works
The GSK3 hypothesis of Alzheimer’s disease
Hooper, C., Killick, R., & Lovestone, S. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05194.x · Cited by 1,191 · see citing works
Tau pathology in Alzheimer disease and other tauopathies
Iqbal, K., del C. Alonso, A., Chen, S., Chohan, M. O., El-Akkad, E., Gong, C.-X., Khatoon, S., Li, B., Liu, F., Rahman, A., et al. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.09.008 · Cited by 1,037 · see citing works
Mechanisms of tau-induced neurodegeneration
Iqbal, K., Liu, F., Gong, C.-X., Alonso, A. D. C., & Grundke-Iqbal, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0486-3 · Cited by 628 · see citing works
Tau phosphorylation in neuronal cell function and dysfunction
Johnson, G. V. W., & Stoothoff, W. H. (2004) · Journal of Cell Science · doi:10.1242/jcs.01558 · Cited by 624 · see citing works
Self-citationThe importance of tau phosphorylation for neurodegenerative diseases
Noble, W., Hanger, D. P., Miller, C. C. J., & Lovestone, S. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00083 · Cited by 475 · see citing works
Ghosh, S., Wu, M. D., Shaftel, S. S., Kyrkanides, S., LaFerla, F. M., Olschowka, J. A., & O'Banion, M. K. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4361-12.2013 · Cited by 390 · see citing works
Histone deacetylase 6 interacts with the microtubule‐associated protein tau
Ding, H., Dolan, P. J., & Johnson, G. V. W. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05564.x · Cited by 387 · see citing works
Self-citationAlquezar, C., Arya, S., & Kao, A. W. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.595532 · Cited by 367 · see citing works
The Roles of Cyclin-dependent Kinase 5 and Glycogen Synthase Kinase 3 in Tau Hyperphosphorylation
Plattner, F., Angelo, M., & Giese, K. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603469200 · Cited by 340 · see citing works
Cripps, D., Thomas, S. N., Jeng, Y., Yang, F., Davies, P., & Yang, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512786200 · Cited by 312 · see citing works
Microtubule-associated protein tau is essential for long-term depression in the hippocampus
Kimura, T., Whitcomb, D. J., Jo, J., Regan, P., Piers, T., Heo, S., Brown, C., Hashikawa, T., Murayama, M., Seok, H., et al. (2014) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2013.0144 · Cited by 307 · see citing works
Overexpression of Dyrk1A contributes to neurofibrillary degeneration in down syndrome
Liu, F., Liang, Z., Wegiel, J., Hwang, Y., Iqbal, K., Grundke‐Iqbal, I., Ramakrishna, N., & Gong, C. (2008) · The FASEB Journal · doi:10.1096/fj.07-104539 · Cited by 272 · see citing works
Durairajan, S. S. K., Liu, L.-F., Lu, J.-H., Chen, L.-L., Yuan, Q., Chung, S. K., Huang, L., Li, X.-S., Huang, J.-D., & Li, M. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.02.016 · Cited by 271 · see citing works
Ochalek, A., Mihalik, B., Avci, H. X., Chandrasekaran, A., Téglási, A., Bock, I., Giudice, M. L., Táncos, Z., Molnár, K., László, L., et al. (2017) · Alzheimer's Research & Therapy · doi:10.1186/s13195-017-0317-z · Cited by 225 · see citing works
Kirouac, L., Rajic, A. J., Cribbs, D. H., & Padmanabhan, J. (2017) · eneuro · doi:10.1523/eneuro.0149-16.2017 · Cited by 207 · see citing works
Modeling Sporadic Alzheimer's Disease in Human Brain Organoids under Serum Exposure
Chen, X., Sun, G., Tian, E., Zhang, M., Davtyan, H., Beach, T. G., Reiman, E. M., Blurton‐Jones, M., Holtzman, D. M., & Shi, Y. (2021) · Advanced Science · doi:10.1002/advs.202101462 · Cited by 200 · see citing works
Nisbet, R. M., Van der Jeugd, A., Leinenga, G., Evans, H. T., Janowicz, P. W., & Götz, J. (2017) · Brain · doi:10.1093/brain/awx052 · Cited by 187 · see citing works
GSK‐3 in Neurodegenerative Diseases
Lei, P., Ayton, S., Bush, A. I., & Adlard, P. A. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/189246 · Cited by 177 · see citing works
Chow, H.-M., Shi, M., Cheng, A., Gao, Y., Chen, G., Song, X., So, R. W. L., Zhang, J., & Herrup, K. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0505-1 · Cited by 171 · see citing works
Funk, K. E., Thomas, S. N., Schafer, K. N., Cooper, G. L., Liao, Z., Clark, D. J., Yang, A. J., & Kuret, J. (2014) · Biochemical Journal · doi:10.1042/bj20140372 · Cited by 142 · see citing works
Cavallini, A., Brewerton, S., Bell, A., Sargent, S., Glover, S., Hardy, C., Moore, R., Calley, J., Ramachandran, D., Poidinger, M., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.463984 · Cited by 133 · see citing works
Alzheimer’s disease: Ablating single master site abolishes tau hyperphosphorylation
Stefanoska, K., Gajwani, M., Tan, A. R. P., Ahel, H. I., Asih, P. R., Volkerling, A., Poljak, A., & Ittner, A. (2022) · Science Advances · doi:10.1126/sciadv.abl8809 · Cited by 128 · see citing works
The potential therapeutic effects of THC on Alzheimer’s disease
Cao, C., Li, Y., Liu, H., Bai, G., Mayl, J., Lin, X., Sutherland, K., Nabar, N., & Cai, J. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140093 · Cited by 121 · see citing works
Hernandez, P., Lee, G., Sjoberg, M., & Maccioni, R. B. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-0933 · Cited by 107 · see citing works
Galas, M.-C., Dourlen, P., Bégard, S., Ando, K., Blum, D., Hamdane, M., & Buée, L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601849200 · Cited by 97 · see citing works
Iijima-Ando, K., Zhao, L., Gatt, A., Shenton, C., & Iijima, K. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq068 · Cited by 72 · see citing works
Role of GSK-3β Inhibitors: New Promises and Opportunities for Alzheimer’s Disease
Shri, S. R., Manandhar, S., Nayak, Y., & Pai, K. S. R. (2023) · Advanced Pharmaceutical Bulletin · doi:10.34172/apb.2023.071 · Cited by 71 · see citing works
Pseudohyperphosphorylation Has Differential Effects on Polymerization and Function of Tau Isoforms
Combs, B., Voss, K., & Gamblin, T. C. (2011) · Biochemistry · doi:10.1021/bi2010569 · Cited by 41 · see citing works
Tau; One Protein, So Many Diseases
Tabeshmehr, P., & Eftekharpour, E. (2023) · Biology · doi:10.3390/biology12020244 · Cited by 33 · see citing works
- Authors
- Cho, J.-H., & Johnson, G. V. W.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Johnson, Gail V.W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 278
- Issue
- 1
- Pages
- 187-193
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2091014617
- Cited by
- 266
- References
- 5
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 16 · 2020: 11 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 2 · 2015: 13 · 2014: 14 · 2013: 15 · 2012: 6
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns035060-07)
- National Institute of Neurological Disorders and Stroke (NS35060)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- glycogen synthase kinase-3β, tau protein, CDK5/p25, tau phosphorylation, microtubule-associated proteins
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Animals, Epitopes, Binding Sites, Cell Fractionation, Cricetinae, Microtubules, Mutation, Phosphorylation, Protein Binding, Recombinant Proteins, CHO Cells, tau Proteins, Glycogen Synthase Kinase 3
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
