To gain insight into the abnormal phosphorylation of PHF-tau, we have determined the phosphorylation sites by identifying phosphopeptides by means of ion spray mass spectrometry followed by sequencing of ethanethiol-modified peptides. Nineteen sites have been identified; all but Ser-262 are localized to the amino- and carboxyl-terminal flanking regions of the microtubule-binding domain. Eleven sites correspond to fetal type sites. Unexpectedly, 10 are non-proline-directed, whereas the others are proline-directed. Thus, the abnormal phosphorylation of PHF-tau can be considered to consist of fetal type phosphorylation and additional proline-directed and non-proline-directed phosphorylation. This non-fetal type phosphorylation may provide PHF-tau with the unusual characteristics.

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				S. E. Merrick, J. Q. Trojanowski, and V. M.-Y. Lee Selective Destruction of Stable Microtubules and Axons by Inhibitors of Protein Serine/Threonine Phosphatases in Cultured Human Neurons (NT2N Cells) J. Neurosci., August 1, 1997; 17(15): 5726 - 5737. [Abstract] [Full Text] [PDF]

				S. Ch. Papasozomenos The heat shock-induced hyperphosphorylation of tau  is estrogen-independent and prevented by androgens: Implications for Alzheimer disease PNAS, June 24, 1997; 94(13): 6612 - 6617. [Abstract] [Full Text] [PDF]

				M. G. Spillantini, M. Goedert, R. A. Crowther, J. R. Murrell, M. R. Farlow, and B. Ghetti Familial multiple system tauopathy with presenile dementia: A disease with abundant neuronal and glial tau filaments PNAS, April 15, 1997; 94(8): 4113 - 4118. [Abstract] [Full Text] [PDF]

				J. Leger, M. Kempf, G. Lee, and R. Brandt Conversion of Serine to Aspartate Imitates Phosphorylation-induced Changes in the Structure and Function of Microtubule-associated Protein Tau J. Biol. Chem., March 28, 1997; 272(13): 8441 - 8446. [Abstract] [Full Text] [PDF]

				M. Goedert The Neurofibrillary Pathology of Alzheimer's Disease Neuroscientist, March 1, 1997; 3(2): 131 - 141. [Abstract] [PDF]

				HannoM. Roder, R.P. Fracasso, FrederickJ. Hoffman, J. A. Witowsky, G. Davis, and C. B. Pellegrino Phosphorylation-dependent Monoclonal Tau Antibodies Do Not Reliably Report Phosphorylation by Extracellular Signal-regulated Kinase 2at Specific Sites J. Biol. Chem., February 14, 1997; 272(7): 4509 - 4515. [Abstract] [Full Text] [PDF]

				H. K. Paudel and H. K. Paudel The Regulatory Ser262 of Microtubule-associated Protein Tau Is Phosphorylated by Phosphorylase Kinase J. Biol. Chem., January 17, 1997; 272(3): 1777 - 1785. [Abstract] [Full Text] [PDF]

				C. S. Arnold, G. V.W. Johnson, R. N. Cole, D. L.-Y. Dong, M. Lee, and G. W. Hart The Microtubule-associated Protein Tau Is Extensively Modified with O-linked N-acetylglucosamine J. Biol. Chem., November 15, 1996; 271(46): 28741 - 28744. [Abstract] [Full Text] [PDF]

				S. E. Merrick, D. C. Demoise, and V. M.-Y. Lee Site-specific Dephosphorylation of Tau Protein at Ser[IMAGE]/Thr[IMAGE] in Response to Microtubule Depolymerization in Cultured Human Neurons Involves Protein Phosphatase 2A J. Biol. Chem., March 8, 1996; 271(10): 5589 - 5594. [Abstract] [Full Text] [PDF]

				M. Goedert, M.G. Spillantini, M. Hasegawa, R. Jakes, R.A. Crowther, and A. Klug Molecular Dissection of the Neurofibrillary Lesions of Alzheimer's Disease Cold Spring Harb Symp Quant Biol, January 1, 1996; 61(0): 565 - 573. [Abstract] [PDF]

				P. Seubert, M. Mawal-Dewan, R. Barbour, R. Jakes, M. Goedert, G. V. W. Johnson, J. M. Litersky, D. Schenk, I. Lieberburg, J. Q. Trojanowski, et al. Detection of Phosphorylated Ser[IMAGE] in Fetal Tau, Adult Tau, and Paired Helical Filament Tau J. Biol. Chem., August 11, 1995; 270(32): 18917 - 18922. [Abstract] [Full Text] [PDF]

				J.-Z. Wang, C.-X. Gong, T. Zaidi, I. Grundke-Iqbal, and K. Iqbal Dephosphorylation of Alzheimer Paired Helical Filaments by Protein Phosphatase-2A and -2B J. Biol. Chem., March 3, 1995; 270(9): 4854 - 4860. [Abstract] [Full Text] [PDF]

				T. Maas, J. Eidenmuller, and R. Brandt Interaction of Tau with the Neural Membrane Cortex Is Regulated by Phosphorylation at Sites That Are Modified in Paired Helical Filaments J. Biol. Chem., May 19, 2000; 275(21): 15733 - 15740. [Abstract] [Full Text] [PDF]

				K. Sobue, A. Agarwal-Mawal, W. Li, W. Sun, Y. Miura, and H. K. Paudel Interaction of Neuronal Cdc2-like Protein Kinase with Microtubule-associated Protein Tau J. Biol. Chem., May 26, 2000; 275(22): 16673 - 16680. [Abstract] [Full Text] [PDF]

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				K. Spittaels, C. Van den Haute, J. Van Dorpe, H. Geerts, M. Mercken, K. Bruynseels, R. Lasrado, K. Vandezande, I. Laenen, T. Boon, et al. Glycogen Synthase Kinase-3beta Phosphorylates Protein Tau and Rescues the Axonopathy in the Central Nervous System of Human Four-repeat Tau Transgenic Mice J. Biol. Chem., December 22, 2000; 275(52): 41340 - 41349. [Abstract] [Full Text] [PDF]

				T. Taniguchi, T. Kawamata, H. Mukai, H. Hasegawa, T. Isagawa, M. Yasuda, T. Hashimoto, A. Terashima, M. Nakai, Y. Ono, et al. Phosphorylation of Tau Is Regulated by PKN J. Biol. Chem., March 23, 2001; 276(13): 10025 - 10031. [Abstract] [Full Text] [PDF]

				N. Sawamura, J.-S. Gong, W. S. Garver, R. A. Heidenreich, H. Ninomiya, K. Ohno, K. Yanagisawa, and M. Michikawa Site-specific Phosphorylation of Tau Accompanied by Activation of Mitogen-activated Protein Kinase (MAPK) in Brains of Niemann-Pick Type C Mice J. Biol. Chem., March 23, 2001; 276(13): 10314 - 10319. [Abstract] [Full Text] [PDF]

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				A. del C. Alonso, T. Zaidi, M. Novak, H. S. Barra, I. Grundke-Iqbal, and K. Iqbal Interaction of Tau Isoforms with Alzheimer's Disease Abnormally Hyperphosphorylated Tau and in Vitro Phosphorylation into the Disease-like Protein J. Biol. Chem., October 5, 2001; 276(41): 37967 - 37973. [Abstract] [Full Text] [PDF]

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