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PDP - Template Name: Antibody Sampler Kit
PDP - Template ID: *******4a3ef3a
  1. Products /
  2. Primary Antibodies /
  3. Phospho-Tau (Ser214/T217) Signaling Antibody Sampler Kit

Phospho-Tau (Ser214/T217) Signaling Antibody Sampler Kit #89892

    Product Information

    Kit Usage Information

    Protocols

    Product Description

    The Phospho-Tau (Ser214/T217) Signaling Antibody Sampler Kit provides an economical means of detecting the signaling cascade leading to tau phosphorylation at Ser214 and Thr217, using phospho-specific and control antibodies. The kit includes enough antibodies to perform two western blot experiments with each primary antibody.

    Background

    Tau is a heterogeneous microtubule-associated protein that promotes and stabilizes microtubule assembly, especially in axons. Six isoforms with different amino-terminal inserts and different numbers of tandem repeats near the carboxy terminus have been identified, and tau is hyperphosphorylated at approximately 25 sites by Erk, glycogen synthase kinase-3 (GSK-3), and CDK5 (1,2). Phosphorylation decreases the ability of tau to bind to microtubules. Neurofibrillary tangles are a major hallmark of Alzheimer's disease (AD); these tangles are bundles of paired helical filaments (PHFs) composed of hyperphosphorylated tau. Furthermore, research studies have shown that inclusions of tau are found in a number of other neurodegenerative diseases, collectively known as tauopathies (1,3).

    Numerous kinases, including p38 MAPK, JNK, CDK5, GSK3β, and SGK1, have been shown to phosphorylate tau at Ser214, which is found in AD and dementia with Lewy bodies (4-9). p38 MAPK participates in a signaling cascade controlling cellular responses to cytokines and stress and is activated by phosphorylation at Thr180 and Tyr182, allowing for downstream tau Ser214 phosphorylation (10-13). Another kinase that phosphorylates the Ser214 site on tau is the stress-activated protein kinase/Jun-amino-terminal kinase (SAPK/JNK). SAPK/JNK is preferentially activated by a variety of environmental stresses, including UV and gamma radiation, ceramides, inflammatory cytokines, and, in some instances, growth factors and GPCR agonists, which lead to phosphorylation of Thr183 and Tyr185 (14-19).

    Tau phosphorylation at Thr217 has been identified as a highly specific biomarker of AD. Phosphorylated tau at Thr217 can be detected in cerebrospinal fluid in both preclinical and advanced stages of AD and has been shown to successfully differentiate between AD and non-AD neurodegenerative diseases (20,21). One kinase identified to phosphorylate the Thr217 site on tau is p70 S6 kinase (S6K1). S6K1 is a mitogen activated Ser/Thr protein kinase that is required for cell growth and G1 cell cycle progression (22,23). Phosphorylation of Thr389 most closely correlates with S6K1 activity in vivo (24).
    1. Johnson, G.V. and Stoothoff, W.H. (2004) J Cell Sci 117, 5721-9.
    2. Hanger, D.P. et al. (1998) J Neurochem 71, 2465-76.
    3. Bramblett, G.T. et al. (1993) Neuron 10, 1089-99.
    4. Illenberger, S. et al. (1998) Mol Biol Cell 9, 1495-512.
    5. Götz, J. et al. (2001) Science 293, 1491-5.
    6. Yang, Y.C. et al. (2006) Mol Cell Biol 26, 8357-70.
    7. Liu, F. et al. (2006) FEBS Lett 580, 6269-74.
    8. Zhu, B. et al. (2010) Am J Physiol Lung Cell Mol Physiol 299, L493-501.
    9. Duka, V. et al. (2013) PLoS One 8, e75025.
    10. Rouse, J. et al. (1994) Cell 78, 1027-37.
    11. Han, J. et al. (1994) Science 265, 808-11.
    12. Lee, J.C. et al. Nature 372, 739-46.
    13. Freshney, N.W. et al. (1994) Cell 78, 1039-49.
    14. Davis, R.J. (1999) Biochem Soc Symp 64, 1-12.
    15. Ichijo, H. (1999) Oncogene 18, 6087-93.
    16. Kyriakis, J.M. and Avruch, J. (2001) Physiol Rev 81, 807-69.
    17. Kyriakis, J.M. (1999) J Biol Chem 274, 5259-62.
    18. Leppä, S. and Bohmann, D. (1999) Oncogene 18, 6158-62.
    19. Whitmarsh, A.J. and Davis, R.J. (1998) Trends Biochem Sci 23, 481-5.
    20. Barthélemy, N.R. et al. (2020) Alzheimers Res Ther 12, 26.
    21. Janelidze, S. et al. (2020) Nat Commun 11, 1683.
    22. Pullen, N. and Thomas, G. (1997) FEBS Lett 410, 78-82.
    23. Dufner, A. and Thomas, G. (1999) Exp Cell Res 253, 100-9.
    24. Weng, Q.P. et al. (1998) J Biol Chem 273, 16621-9.

    Database Links

    UniProt ID: Q16539 , P45983 , O15264 , P53778 , P10636-8 , P23443 , Q15759


    Entrez-Gene Id: 1432 , 5599 , 5603 , 6300 , 4137 , 6198 , 5600


    Limited Uses

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    For Research Use Only. Not For Use In Diagnostic Procedures.
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