Sequential phosphorylation of Tau by glycogen synthase kinase-3β and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation

European Journal of Biochemistry

Volumn 252, Issue 3, 1998, Pages 542-552

  Zheng Fischhöfer, Qingyi ^a   Biernat, Jacek ^a   Mandelkow, Eva Maria ^a   Illenberger, Susanne ^a   Godemann, Robert ^a   Mandelkow, Eckhard ^a  

^a MAX PLANCK UNIT FOR STRUCTURAL MOLECULAR BIOLOGY   (Germany)

Author keywords

Alzheimer; Epitope mapping; Microtuble associated protein; Phosphorylation; Tau

Indexed keywords

CYCLIC AMP DEPENDENT PROTEIN KINASE; HEPARIN; MONOCLONAL ANTIBODY; POLYANION; POLYGLUTAMIC ACID; PROTEIN KINASE; RNA; TAU PROTEIN;

ALZHEIMER DISEASE; ANIMAL TISSUE; ARTICLE; BRAIN TISSUE; EPITOPE MAPPING; HUMAN; HUMAN TISSUE; MOUSE; NONHUMAN; PAIRED HELICAL FILAMENT; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN PHOSPHORYLATION;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; AMYLOID BETA-PROTEIN; ANTIBODIES, MONOCLONAL; BRAIN; CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASE; CLONING, MOLECULAR; CYCLIC AMP-DEPENDENT PROTEIN KINASES; EPITOPES; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASES; HUMANS; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; PEPTIDE MAPPING; PHOSPHOPEPTIDES; PHOSPHORYLATION; POINT MUTATION; PROTEIN STRUCTURE, SECONDARY; RECOMBINANT PROTEINS; SERINE; SUBSTRATE SPECIFICITY; TAU PROTEINS; THREONINE;

ANIMALIA; INSECTA;

EID: 0032521599     PISSN: 00142956     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1432-1327.1998.2520542.x     Document Type: Article

References (78)

1. Archer, S. J., Vinson, V. K., Pollard, T. D. & Torchia, D. A. (1994) Elucidation of the poly-L-proline binding site in Acanthamoeba profilin-I by NMR spectroscopy. FEBS Lett. 337, 145-151.
2. Baumann, K., Mandelkow, E.-M., Biernat, J., Piwnica-Worms, H. & Mandelkow, H. (1993) Abnormal Alzheimer-like phosphorylation of tau protein by cyclin-dependent kinases cdk2 and cdk5, FEBS Lett. 336, 417-424.
3. Biernat, J., Mandelkow, E.-M., Schröten, C., Lichtenberg-Kraag, B., Steiner, B., Berling, B., Meyer, H. E., Mercken, M., Vandermeeren, A., Goedert, M. & Mandelkow, E. (1992) The switch of tau protein to an Alzheimer-like state includes the phosphorylation of two serine-proline motifs upstream of the microtubule binding region. EMBO J. 11, 1593-1597.
4. Biernat, J., Gustke, N., Drewes, G., Mandelkow, E.-M. & Mandelkow, E. (1993) Phosphorylation of serine 262 strongly reduces the binding of tau protein to microtubules: distinction between PHF-like immunoreactivity and microtubule binding, Neuron 11, 153-163.
5. Binder, L. I., Frankfurter, A. & Rebhun, L. (1985) The distribution of tau in the mammalian central nervous system, J. Cell Biol. 101, 1371-1378.
6. Boyle, W. J., van der Geer, P. & Hunter, T. (1991) Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin layer cellulose plates, Methods Enzymol. 201, 110-149.
7. Braak, E., Braak, H. & Mandelkow, E.-M. (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads, Acta Neuropath. 87, 554-567.
8. Bramblett, G. T., Goedert, M., Jakes, R., Merrick, S. E., Trojanowski, J. Q. & Lee, V. M. Y. (1993) Abnormal tau phosphorylation at Ser(396) in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron 10, 1089-1099.
9. Brandt, R., Lee, G., Teplow, D. B., Shalloway, D. & Abdelghany, M. (1994) Differential effect of phosphorylation and substrate modulation on tail's ability to promote microtubule growth and nucleation. J. Biol. Chem. 269, 11776-11782.
10. Brion, J. P., Smith, C., Couck, A. M., Gallo, J. M. & Anderton, B. H. (1993) Developmental changes in tan phosphorylation: Fetal tau is transiently phosphorylated in a manner similar to paired helical filament tau characteristic of Alzheimers disease. J Neurochem. 61, 2071-2080.
11. Butler, M. & Shelanski, M. L. (1986) Microheterogeneity of microtuhule-associated tan-proteins is due to differences in phosphorylation. J. Neurochem. 47, 1517-1522.
12. Carmel, G., Mager, E. M., Binder, L. I. & Kuret, J. (1996) The structural basis of monoclonal-antibody alz50s selectivity for Alzheimers-disease pathology, J. Biol. Chem. 271, 32789-32795.
13. Correas, I., Diaznido, J. & Avila, J. (1992) Microtubule associated protein tau is phosphorylated by protein kinase C on its tubulin binding domain, J. Biol. Chem. 267, 15721-15728.
14. Drechsel, D. N., Hyman, A. A., Cobb, M. H. & Kirschner, M. W. (1992) Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein Tau, Mol. Biol. Cell 3, 1141-1154.
15. Drewes, G., Lichtenberg-Kraag, B., Döring, F., Mandelkow, E.-M., Biernat, J., Goris, J. & Doree, M. & Mandelkow, E. (1992) Mitogen-activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state, EMBO J. 11, 2131-2138.
16. Drewes, G., Trinczek, B., Illenberger, S., Biernat, J., Schmitt-Ulms, G., Meyer, H. E., Mandelkow, E.-M. & Mandelkow, E. (1995) MAP/ microtubule affinity regulating kinase (P110/mark): a novel protein kinase that regulates tau- microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262, J. Biol. Chem. 270, 7679-7688.
17. Goedert, M., Spillantini, M., Jakes, R., Rutherford, D. & Crowther, R. A. (1989) Multiple isoforms of human microtubule-associated protein-tau: sequences and localization in neurofibrillary tangles of Alzheimers-disease, Neuron 3, 519-526.
18. Goedert, M., Jakes, R., Crowther, R. A., Cohen, P., Vanmechelen, E., Vandermeeren, M. & Cras, P. (1994) Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimers disease: identification of phosphorylation sites in tau protein, Biochem. J. 301, 871-877.
19. Goedert, M., Jakes, R. & Vanmechelen, E. (1995) Monoclonal antibody AT8 recognizes tau protein phosphorylated at both serine 202 and threonine 205, Neurosci. Lett. 189, 167-170.
20. Goedert, M., Jakes, R., Spillantini, M. G., Hasegawa, M., Smith, M. J. & Crowther, R. A. (1996) Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulfated glycosaminoglycans, Nature 383, 550-553.
21. Goode, B. L., Denis, P. E., Panda, D., Radeke, M. J., Miller, H. P., Wilson, L. & Feinstein, S. C. (1997) Functional interactions between the proline-rich and repeat regions of tau-enhance microtubule-binding and assembly, Mol. Biol. Cell 8, 353-365.
22. Greenberg, S. G. & Davies, P (1990) A preparation of Alzheimer paired helical filaments that displays distinct tau protein by polyacrylamide gel electrophoresis, Proc. Natl Acad. Sci. USA 87, 5827-5831.
23. Greenberg, S. G., Davies, P., Schein, J. D. & Binder, L. I. (1992) Hydrofluoric acid-treated tau-PHF proteins display the same biochemical properties as normal tau, J. Biol. Chem. 267, 564-569.
24. Grundke-Iqbal, I., Iqbal, K., Tung, Y., Quinlan, M., Wisniewski, H. & Binder, L. (1986) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology, Proc. Natl Acad. Sci. USA 83, 4913-4917.
25. Gustke, N., Steiner, B., Mandelkow, E.-M., Biernat, J., Meyer, H. E., Goedert, M. & Mandelkow, E. (1992) The Alzheimer-like phosphorylation of tau protein reduces microtubule binding and involves SerPro and Thr-Pro motifs, FEBS Lett. 307, 199-205.
26. Gustke, N., Trinczek, B., Biernat, J., Mandelkow, E.-M. & Mandelkow, E. (1994) Domains of Tau protein and interactions with microtubules, Biochemistry 33, 9511-9522.
27. Hagestedt, T., Lichtenberg, B., Wille, H. & Mandelkow, E.-M. & Mandelkow, E. (1989) Tau protein becomes long and stiff upon phosphorylation: correlation between paracrystalline structure and degree of phosphorylation, J. Cell Biol. 109, 1643-1651.
28. Hanger, D., Hughes, K., Woodgett, J., Brion, J. & Anderton, B. (1992) Glycogen-synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localization of the kinase, Neurosci. Lett. 147, 58-62.
29. Hasegawa, M., Watanabe, A., Takio, K., Suzuki, M., Arai, T., Titani, K. & Ihara, Y. (1993) Characterization of two distinct monoclonal antibodies to paired helical filaments: Further evidence for fetal-type phosphorylation of tau in paired helical filaments, J. Neurochem. 60, 2068-2077.
30. Hoffmann, R., Lee, V. M. Y., Leight, S., Varga, I. & Otvos, L. (1997) Unique Alzheimer's disease paired helical filament specific epitopes involve double phosphorylation at specific sites, Biochemistry 36, 8114-8124.
31. Hong, M., Chen, D. C. R. & Klein, P. S. & Lee, V. M. Y. (1997) Lithium reduces tau phosphorylation by inhibition of glycogen-synthase kinase-3, J. Biol. Chem. 272, 25326-25332.
32. Illenberger, S., Drewes, G., Trinczek, B., Biernat, J., Meyer, H. E., Olmsted, J. B., Mandelkow, E.-M. & Mandelkow, E. (1996) Phosphorylation of microtubule-associated proteins MAP2 and MAP4 by the protein kinase pi 10/MARK: phosphorylation sites and regulation of microtubule dynamics, J. Biol. Chem. 271, 10834-10843.
33. Illenberger, S., Zheng-Fischhöfer, Q., Preuss, U., Stamer, K., Baumann, K. & Mandelkow, E. (1998) The endogeneous and cell-cycle dependent phosphorylation of the microtubule-associated protein tau in living cells: implications for Alzheimer's disease, Mol. Biol. Cell, in the press.
34. Ishiguro, K., Shiratsuchi, A., Sato, S., Omori, A., Arioka, M., Kobayashi, S., Uchida, T. & Imuhori, K. (1993) Glycogen-synthase kinase 3-beta is identical to tau protein kinase I generating several epitopes of paired helical filaments, FEBS Lett. 325, 167-172.
35. Ishiguro, K., Sato, K., Takamatsu, M., Park, J., Uchida, T. & Imahori, K. (1995) Analysis of phosphorylation of tau with antibodies specific for phosphorylation sites, Neurosci. Lett. 202, 81-84.
36. Jicha, G. A., Bowser, R., Kazam, I. G. & Davies, P. (1997) Alz-50 and MC-1, a new monoclonal-antibody raised to paired helical filaments. recognize conformational epitopes on recombinant-tau, J. Neurosci. Res. 48, 128-132.
37. Johnson, G. & Jenkins, S. (1996) Tau protein and Alzheimer's disease brain, Alzheimer's Disease Rev. 1, 38-54.
38. Kampers, T., Friedhoff, P., Biernat, J., Mandelkow, E.-M. & Mandelkow, E. (1996) RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments. FEBS Lett. 399, 344-349.
39. Kanemaru, K., Takio, K., Miura, R., Titani, K. & Ihara, Y. (1992) Fetal-type phosphorylation of the tau in paired helical filaments, J. Neurochem. 58, 1667-1675.
40. Köpke, E., Tung, Y., Shaikh, S., Alonso, A., Iqbal, K. & Grundke-Iqbal, I. (1993) Microtubule-associated protein tau: Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer's disease. J. Biol. Chem. 268, 24374-24384.
41. Kosik, K. S. & Greenberg, S. M. (1994) Tau protein and Alzheimer disease, in Alzheimer Disease (Terry, R., Katzman, R. & Bick, K., eds) pp. 335-344, Raven Press, New York.
42. Ksiezak-Reding, H., Liu, W. K. & Yen, S. H. (1992) Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments, Brain Res. 597, 209-219.
43. Lee, V. M. Y., Balin, B. J., Otvos, L. & Trojanowski, J. Q. (1991) A68 - a major subunit of paired helical filaments and derivatized forms of normal tau, Science 251, 675-678.
44. Lichtenberg-Kraag, B., Mandelkow, E.-M., Biernat, J., Steiner, B., Schröter, C., Gustke, N., Meyer, H. E. & Mandelkow, E. (1992) Phosphorylation dependent interaction of neurofilament antibodies with tau protein: epitopes, phosphorylation sites, and relationship with Alzheimer tau, Proc. Natl Acad. Sci. USA 89, 5384-5388.
45. Litersky, J. M. & Johnson, G. V. W. (1992) Phosphorylation by cAMP-dependent protein kinase inhibits the degradation of tau by calpain, J. Biol. Chem. 267, 1563-1568.
46. Lovestone, S., Reynolds, C. H., Latimer, D., Davis, D. R., Anderton, B. H., Gallo, J. M., Hanger, D., Mulot, S., Marquardt, B., Stabel, S., Woodgett, J. R. & Miller, C. C. J. (1994) Alzheimers disease-like phosphorylation of the microtubule-associated protein tau by glycogen-synthase kinase-3 in transfected mammalian-cells, Curr. Biol. 4, 1077-1086.
47. Mandelkow, E.-M., Drewes, G., Biernat, J., Gustke, N., Van Lint, J. & Vandenheede, J. R. & Mandelkow, E. (1992) Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau, FEBS Lett. 314, 315-321.
48. Mandelkow, E.-M., Biernat, J., Drewes, G., Gustke, N., Trinczek, B. & Mandelkow, E. (1995) Tau domains, phosphorylation, and interactions with microtubules, Neurobiol. Aging 16, 355-362.
49. Matsuo, E. S., Shin, R. W., Billingsley, M. L., Vandevoorde, A., O'Connor, M., Trojanowski, J. Q. & Lee, V. M. Y. (1994) Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau, Neuron 13, 989-1002.
50. Mercken, M., Vandermeeren, M., Lubke, U., Six, J., Boons, J., Van de Voorde, A. & Martin, J.-J. & Gheuens, J. (1992) Monoclonal antibodies with selective specificity for Alzheimer tau are directed against phosphatase-sensitive epitopes. Acta Neuropathol. 84, 265-272.
51. Mercken, M., Grynspan, F. & Nixon, R. A. (1995) Differential sensitivity proteolysis by brain calpain of adult human Tau, fetal human tau and PHF Tau, FEBS Lett. 368, 10-14.
52. Meyer, H. E., Eisermann, B., Heber, M., Hoffmann-Posorske, E., Korte, H., Weigt, C., Wegner, A., Hutton, T., Donella-Deana, A. & Perich, J. W. (1993) Strategies for nonradioactive methods in the localization of phosphorylated amino-acids in proteins. FASEB J. 7, 776-782.
53. Moreno, F. J., Munoz-Montano, J. R. & Avila, J. (1996) Glycogen synthase kinase-3 phosphorylation of different residues in the presence of different factors: analysis on tau protein. Mol. Cell. Biochem. 165, 47-54.
54. Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Yoshida, H., Titani, K. & Ihara, Y. (1995) Proline-directed and non-proline-directed phosphorylation of PHF-Tau, J. Biol. Chem. 270, 823-829.
55. Musacchio, A., Saraste, M. & Wilmanns, M. (1994) High-resolution crystal-structures of tyrosine kinase SH3 domains complexed with proline-rich peptides, Nat. Struct. Biol. 1, 546-551.
56. Otvos, L., Feiner, L., Lang, E., Szendrei, G., Goedert, M. & Lee, V. M. Y. (1994) Monoclonal antibody PHF-1 recognizes tau protein phosphorylated at serine residue 396 and 404, J. Neurosci. Res. 39, 669-673
57. Paudel, H., Lew, J., Ali, Z. & Wang, J. (1993) Brain proline-directed protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments, J. Biol. Chem. 268, 23512-23518.
58. Pearson, R. B. & Kemp, B. E. (1991) Protein kinase phosphorylation site sequences and consensus specificity motifs, Methods Enzymol. 200, 62-81.
59. Perez, M., Valpuesta, J. M., Medina, M., Degarcini, E. M. & Avila, J. (1996) Polymerization of tau into filaments in the presence of heparin: the minimal sequence required for tau-tau-interaction, J. Neurochem. 67, 1183-1190.
60. Schägger, H. & von Jagow, G. (1987) Tricine-sodium dodecyl sulfute-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa, Anal. Biochem. 166, 368-379.
61. Schweers, O., Schonbrunn, E., Marx, A. & Mandelkow, E. (1994) Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta structure, J. Biol. Chem. 269, 24290-24297.
62. Scott, C., Spreen, R., Herman, J., Chow, F., Davison, M., Young, J. & Caputo, C. (1993) Phosphorylation of recombinant tau by cAMP-dependent protein kinase: identification of phosphorylation sites and effect on microtubule assembly, J. Biol. Chem. 268, 1166-1173.
63. Seubert, P., Mawaldewan, M., Barbour, R., Jakes, R., Goedert, M., Johnson, G. V. W., Litersky, J., Schenk, D., Lieberburg, I., Trojanowski, J. & Lee, V. M. Y. (1995) Detection of phosphorylated Ser(262) in fetal tau, adult tau, and paired helical filament tau, J. Biol. Chem. 270, 18917-18922.
64. Singh, T. J., Haque, N., Grundke-Iqbal, I. & Iqbal, K. (1995) Rapid Alzheimer-like phosphorylation of tau by the synergistic actions of non-proline-dependent protein-kinases and GSK-3, FEBS Lett. 358, 267-272.
65. Skurat, A. V. & Roach, P. J. (1996) Multiple mechanisms for the phosphorylation of C-terminal regulatory sites in rabbit muscle glycogen synthase expressed in COS cells, Biochem. J. 313, 45-50.
66. Song, J. S. & Yang, S. D. (1995) Tau-protein kinase-1 (GSK-3-beta, kinase Fa) in heparin phosphorylates tau on Serf(199), Thr(231), Ser(235), Ser(262) Ser(369), and Ser(400) sites phosphorylated in Alzheimer-disease brain, J. Protein. Chem. 14, 95-105.
67. Stambolic, V., Ruel, L. & Woodgett, J. R. (1996) Lithium inhibits glycogen-synthase kinase-3 activity and mimics wingless signaling in intact cells, Curr. Biol. 6, 1664-1668.
68. Steiner, B., Mandelkow, E.-M., Biernat, J., Gustke, N., Meyer, H. E., Schmidt, B., Mieskes, G., Söling, H. D., Drechsel, D., Kirschner, M. W., Goedert, M. & Mandelkow, E. (1990) Phosphorylation of microtubule-associated protein tau: Identification of the site for Ca+ +-calmodulin dependent kinase and relationship with tau phosphorylation in Alzheimer tangles, EMBO J. 9, 3539-1544.
69. Sternberger, N. H. & Sternberger, L. A. & Ulrich, J. (1985) Aberrant neurofilament phosphorylation in Alzheimer's disease, Proc. Natl Acad. Sci. USA 82, 4274-4276.
70. Studier, W. F., Rosenberg, A. H., Dunn, J. J. & Duhendorff, J. W. (1990) Use of T7 RNA polymerase to direct the expression of cloned genes. Methods Enzymol. 185, 60-89.
71. Sutherland, C., Campbell, D. G. & Cohen, P. (1993) Identification of insulin-stimulated protein kinase-1 as the rabbit equivalent of rsk90-2. Identification of two threonines phosphorylated during activation by mitogen-activated protein-kinase, Eur. J. Biochem. 212, 581-588.
72. Szendrei, G., Lee, V. M. Y. & Otvos, L. (1993) Recognition of the minimal epitope of monoclonal antibody Tau-1 depends upon the presence of a phosphate group hut not its location, J. Neurosci. Res. 34, 243-249.
73. Trinczek, B., Biernat, J., Baumann, K., Mandelkow, E.-M. & Mandelkow, E. (1995) Domains of tau protein, differential phosphorylation, and dynamic instability of microtubules, Mol. Biol. Cell 6, 1887-1902.
74. Vulliet, R., Halloran, S., Braun, R., Smith, A. & Lee, G. (1992) Proline-directed phosphorylation of human tau protein. J. Biol. Chem. 267, 22570-22574.
75. Watanabe, A., Hasegawa, M., Suzuki, M., Takio, K., Morishima-Kawashima, M., Titani, K., Arai, K., Kosik, K. & Ihara, Y. (1993) In vivo phosphorylation sites in fetal and adult rat tau, J. Biol. Chem. 268, 25712-25717.
76. Wessel, D. & Flügge, U. I. (1984) A method for quantitative recovery of protein in dilute solution in the presence of detergents and lipids, Anal. Biochem. 138, 141-143.
77. Woodgett, J. R. (1995) Glycogen synthase kinase-3, in The protein kinase fact book - protein serine kinases (Hardie, D. G. & Hanks, S., eds) pp. 231-233, Academic Press, San Diego.
78. Yoshida, H. & Ihara, Y. (1993) Tau in paired helical filaments is functionally distinct from fetal tau: assembly incompetence of paired helical filament tau, J. Neurochem 61, 1183- 1186.