Ser396
Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage PhosphoSitePlus® v6.7.1.1
Powered by Cell Signaling Technology
Home > Phosphorylation Site Page: > Ser396  -  Tau iso8 (human)

Site Information
GAEIVyKsPVVsGDt   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449081

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 105 , 107 ) , electrophoretic mobility shift ( 85 ) , immunoassay ( 8 , 11 , 18 , 22 , 27 , 28 , 29 , 33 , 35 , 42 , 53 ) , immunoprecipitation ( 13 , 16 , 26 , 40 ) , mass spectrometry ( 9 , 13 , 17 , 18 , 39 , 57 , 59 , 71 , 76 , 89 , 105 ) , mass spectrometry (in vitro) ( 37 ) , microscopy-colocalization with upstream kinase ( 98 ) , modification-specific antibody ( 16 , 39 , 40 , 59 ) , mutation of modification site ( 13 , 16 , 26 , 40 , 43 , 62 , 63 , 65 , 70 , 83 , 85 , 110 ) , peptide sequencing ( 97 ) , phospho-antibody ( 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 58 , 59 , 63 , 64 , 66 , 67 , 68 , 69 , 71 , 72 , 73 , 74 , 77 , 78 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 91 , 93 , 94 , 95 , 96 , 98 , 100 , 101 , 103 , 106 , 109 , 110 ) , western blotting ( 6 , 7 , 10 , 12 , 13 , 14 , 15 , 16 , 19 , 20 , 21 , 23 , 24 , 25 , 26 , 28 , 30 , 31 , 32 , 34 , 35 , 36 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 48 , 50 , 52 , 53 , 54 , 55 , 56 , 58 , 63 , 64 , 65 , 67 , 68 , 69 , 72 , 74 , 77 , 78 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 88 , 91 , 95 , 97 , 98 , 103 , 105 , 106 , 109 , 110 )
Disease tissue studied:
Alzheimer's disease ( 9 , 47 , 51 , 56 , 57 , 63 , 64 , 66 , 67 , 68 , 76 , 84 , 98 , 100 , 105 ) , adrenal cancer ( 62 , 93 ) , pheochromocytoma ( 62 , 93 ) , brain cancer ( 98 ) , glioma ( 98 ) , neuroblastoma ( 10 , 11 , 15 , 16 , 18 , 20 , 23 , 24 , 25 , 29 , 30 , 34 , 36 , 41 , 78 , 80 , 85 , 103 , 106 , 107 ) , melanoma skin cancer ( 58 ) , diabetes mellitus ( 67 ) , type 2 diabetes ( 67 ) , PSP ( 71 , 88 )
Relevant cell line - cell type - tissue:
'brain, brainstem' ( 72 , 95 ) , 'brain, caudate-putamen' ( 88 ) , 'brain, cerebellum' ( 68 ) , 'brain, cerebral cortex' ( 22 , 35 , 43 , 84 , 88 , 89 , 95 ) , 'brain, embryonic' ( 109 ) , 'brain, hippocampus' ( 13 , 30 , 43 , 72 , 101 ) , 'brain, hippocampus, CA1 region' ( 33 ) , 'brain, hippocampus, dentate gyrus' ( 44 ) , 'brain, striatum' ( 88 ) , 'neuron, cortical' ( 32 , 74 ) , 'neuron, cortical'-brain ( 54 ) , 'neuron, hippocampal, CA1 pyramidal' ( 35 ) , 'neuron, striatal'-brain ( 54 ) , 293 (epithelial) ( 12 , 20 , 32 , 43 , 45 , 48 , 52 , 53 , 56 , 65 , 69 , 83 , 94 ) , 3T3 (fibroblast) ( 31 ) , astrocyte ( 14 , 42 ) , brain ( 7 , 27 , 39 , 45 , 47 , 50 , 55 , 57 , 59 , 67 , 71 , 76 , 91 , 105 , 109 , 110 ) , brain [Tau iso8 (human)] ( 77 , 82 ) , C8D1A (astrocyte) ( 14 ) , cerebrospinal fluid ( 9 , 100 ) , CHO (fibroblast) [Tau (human), transfection] ( 107 ) , CHO (fibroblast) [Tau iso8 (human)] ( 81 ) , CHO (fibroblast) ( 62 , 64 , 78 , 86 , 97 , 110 ) , colon ( 8 ) , COS (fibroblast) ( 84 , 85 ) , E.coli (bacterial) ( 37 , 70 ) , fibroblast ( 21 ) , H4 (glial) ( 98 ) , HEK293T (epithelial) ( 13 , 40 , 46 ) , HeLa (cervical) ( 58 , 73 ) , LAN-5 (neural crest) ( 106 , 107 ) , microglia ( 42 ) , Neuro-2a (neuron) ( 23 , 106 ) , neuron ( 6 , 19 , 20 , 26 , 42 ) , neuron-'brain, cerebral cortex' ( 51 ) , neuron-'brain, hippocampus' ( 35 , 40 , 43 , 58 , 63 , 66 , 85 ) , neuron-brain ( 28 ) , NPC (neural crest) ( 42 ) , PC-12 (chromaffin) ( 62 , 93 ) , SH-SY5Y (neural crest) ( 10 , 11 , 15 , 16 , 18 , 20 , 23 , 24 , 25 , 29 , 30 , 34 , 36 , 41 , 78 , 80 , 85 , 87 , 103 ) , spinal cord ( 44 )

Upstream Regulation
Regulatory protein:
AKAP9 (human) ( 18 ) , APP (human) ( 72 ) , ATG5 (human) ( 24 ) , CASP6 (human) ( 35 ) , CDC37 (human) ( 58 ) , CDK5R1 (mouse) ( 95 ) , Diminuto (human) ( 14 , 34 , 36 ) , ERK5 (human) ( 103 ) , JNK1 (human) ( 85 , 97 ) , MEK5 (human) ( 103 ) , p300 (human) ( 16 ) , P38B (human) ( 13 ) , P38G (human) ( 13 , 103 ) , PTPRA (human) ( 53 ) , RASD1 (human) ( 69 ) , RXRA (mouse) ( 81 ) , SET (human) ( 40 ) , SET (mouse) ( 43 ) , SGK1 (human) ( 30 ) , SPAG5 (human) ( 73 ) , Tau iso8 (human) ( 63 , 78 , 82 ) , TEBP (human) ( 58 )
Putative in vivo kinases:
CDK5 (mouse) ( 95 ) , CK1D (human) ( 94 ) , DYRK1A (human) ( 46 ) , ERK1 (human) ( 14 ) , ERK2 (human) ( 14 ) , GSK3A (human) ( 65 ) , GSK3B (human) ( 10 , 12 , 31 , 32 , 34 , 64 , 65 , 73 , 85 ) , JNK1 (human) ( 85 ) , P38A (human) ( 13 )
Kinases, in vitro:
AMPKA1 (human) ( 60 ) , CAMK2A (rat) ( 108 ) , CDK2 (human) ( 37 ) , CDK5 (human) ( 79 , 99 , 102 ) , CK1D (human) ( 94 ) , DYRK1A (human) ( 46 ) , DYRK1A (rat) ( 75 ) , ERK1 (human) ( 107 ) , ERK2 (human) ( 107 ) , GSK3A (cow) ( 108 ) , GSK3B (human) ( 13 , 37 , 61 , 75 , 79 , 90 , 99 , 104 ) , MARK1 (human) ( 60 ) , P38A (human) ( 13 ) , P38D (human) ( 103 ) , P38G (human) ( 103 ) , PKCA (rat) ( 108 )
Putative upstream phosphatases:
PPP2CA (human) ( 12 , 34 )
Phosphatases, in vitro:
PPP2CA (human) ( 64 )
Treatments:
(E)-4-(3-(2-(5-nitroquinolin-2-yl)vinyl)quinolin-2-yl)morpholine ( 15 ) , 2-(pyridin-4-yl)-4-(p-tolyl)quinoline ( 15 ) , 24r ( 11 ) , 27g ( 11 ) , 2JY-OBZ4 ( 12 ) , AlCl3 ( 23 ) , anisomycin ( 103 ) , apilimod ( 28 ) , arsenite ( 97 ) , ATG1 ( 7 ) , beta-amyloid_25-35 ( 10 , 25 ) , chloroquine ( 86 ) , colforsin ( 56 ) , DES ( 34 ) , development ( 7 , 77 ) , dexamethasone ( 30 ) , DIPQUO ( 31 ) , donepezil ( 11 ) , doxycycline ( 98 ) , EMD638683 ( 30 ) , FK506 ( 77 ) , ginkgolic acid ( 48 ) , glyceraldehyde ( 11 , 29 ) , GW_9662 ( 81 ) , high-fat diet ( 30 ) , high_glucose ( 30 ) , huperzine_A ( 12 ) , IC261 ( 94 ) , JNK_inhibitor_I ( 81 ) , JQ1 ( 19 ) , kenpaullone ( 97 ) , KYP-2047 ( 6 ) , lithium ( 10 , 25 , 73 , 74 , 80 , 85 , 87 , 97 ) , low_glucose ( 93 ) , LY294002 ( 81 ) , macelignan ( 20 ) , MG132 ( 23 , 86 ) , MK-591 ( 55 ) , MOS ( 32 ) , mutation ( 92 ) , myricetin ( 24 ) , nocodazole ( 85 ) , okadaic_acid ( 53 , 56 , 74 , 93 , 97 ) , olomoucine ( 97 ) , PD98059 ( 87 ) , pioglitazone ( 81 ) , PUGNAc ( 93 ) , rolipram ( 18 , 45 ) , SAD-2 ( 11 ) , SAD-6 ( 11 ) , SB202190 ( 103 ) , SB203580 ( 85 , 97 ) , SB216763 ( 80 ) , SB415286 ( 15 ) , seliciclib ( 85 , 97 ) , siRNA ( 31 , 69 ) , sorbitol ( 103 ) , SP600125 ( 85 ) , staurosporine ( 103 ) , streptozotocin ( 93 ) , T0070907 ( 81 ) , tanespimycin ( 86 ) , taxol ( 85 ) , tideglusib ( 29 ) , triciribine ( 81 ) , troglitazone ( 81 ) , tungstate ( 87 ) , U0126 ( 14 , 31 , 97 ) , W5 ( 25 ) , wortmannin ( 81 ) , XJP-1 ( 11 )

Downstream Regulation
Effects of modification on Tau iso8:
intracellular localization ( 98 ) , molecular association, regulation ( 83 , 92 , 94 , 101 , 102 , 110 ) , O-GlcNAc glycosylation ( 68 ) , phosphorylation ( 83 ) , protein conformation ( 37 , 56 , 70 ) , protein processing ( 90 )
Effects of modification on biological processes:
apoptosis, induced ( 24 ) , autophagy, inhibited ( 36 ) , cell differentiation, inhibited ( 31 ) , cell growth, inhibited ( 34 ) , cytoskeletal reorganization ( 70 , 75 , 83 , 98 , 101 , 102 , 110 )
Induce interaction with:
Tau iso8 (human) ( 83 , 92 )
Inhibit interaction with:
TUBA1A (cow) ( 102 ) , TUBA4A (human) ( 83 ) , TUBB (cow) ( 102 ) , TUBB (human) ( 110 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 9 , 21 , 22 , 33 , 35 , 42 , 44 , 49 , 54 , 57 , 66 , 67 , 68 , 70 , 100 , 101 , 105 , 110 ) , ALS ( 109 ) , AGD ( 27 ) , CTE ( 22 ) , DLB ( 54 ) , type 2 diabetes ( 30 , 67 ) , Down syndrome ( 49 ) , Parkinson's disease ( 54 , 109 ) , PSP ( 71 )

References 

1

Hartnell IJ, et al. (2024) Glial reactivity and T cell infiltration in frontotemporal lobar degeneration with tau pathology. Brain 147, 590-606
37703311   Curated Info

2

Chu Y, et al. (2024) Nigrostriatal tau pathology in parkinsonism and Parkinson's disease. Brain 147, 444-457
38006313   Curated Info

3

Nuñez-Diaz C, et al. (2024) The fluorescent ligand bTVBT2 reveals increased p-tau uptake by retinal microglia in Alzheimer's disease patients and App mice. Alzheimers Res Ther 16, 4
38167557   Curated Info

4

Zhang X, et al. (2023) Soluble TREM2 ameliorates tau phosphorylation and cognitive deficits through activating transgelin-2 in Alzheimer's disease. Nat Commun 14, 6670
37865646   Curated Info

5

Isei MO, et al. (2023) Site-specific phosphorylation of tau impacts mitochondrial function and response to stressors. J Neurochem
37787052   Curated Info

6

Eteläinen TS, et al. (2023) A prolyl oligopeptidase inhibitor reduces tau pathology in cellular models and in mice with tauopathy. Sci Transl Med 15, eabq2915
37043557   Curated Info

7

Chatterjee S, et al. (2023) Age-related changes in tau and autophagy in human brain in the absence of neurodegeneration. PLoS One 18, e0262792
36701399   Curated Info

8

Chapelet G, et al. (2023) Tau expression and phosphorylation in enteroendocrine cells. Front Neurosci 17, 1166848
37332860   Curated Info

9

Gobom J, et al. (2022) Antibody-free measurement of cerebrospinal fluid tau phosphorylation across the Alzheimer's disease continuum. Mol Neurodegener 17, 81
36510321   Curated Info

10

Yan N, et al. (2022) Synthesis and biological evaluation of thieno[3,2-]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3β inhibitors for Alzheimer's disease. J Enzyme Inhib Med Chem 37, 1724-1736
35698879   Curated Info

11

Uras G, et al. (2022) Development of p-Tau Differentiated Cell Model of Alzheimer's Disease to Screen Novel Acetylcholinesterase Inhibitors. Int J Mol Sci 23
36499118   Curated Info

12

Guo Q, et al. (2022) Novel small molecular compound 2JY-OBZ4 alleviates AD pathology in cell models via regulating multiple targets. Aging (Albany NY) 14, 8077-8094
36227154   Curated Info

13

Stefanoska K, et al. (2022) Alzheimer's disease: Ablating single master site abolishes tau hyperphosphorylation. Sci Adv 8, eabl8809
35857446   Curated Info

14

Mai M, et al. (2022) DHCR24 Knockdown Induces Tau Hyperphosphorylation at Thr181, Ser199, Ser262, and Ser396 Sites via Activation of the Lipid Raft-Dependent Ras/MEK/ERK Signaling Pathway in C8D1A Astrocytes. Mol Neurobiol
35804281   Curated Info

15

Lin CH, et al. (2022) Virtual Screening and Testing of GSK-3 Inhibitors Using Human SH-SY5Y Cells Expressing Tau Folding Reporter and Mouse Hippocampal Primary Culture under Tau Cytotoxicity. Biomol Ther (Seoul) 31
35790892   Curated Info

16

Kim MS, et al. (2022) Tau acetylation at K280 regulates tau phosphorylation. Int J Neurosci, 1-5
35603448   Curated Info

17

Ferrer I, et al. (2022) Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model. Int J Mol Sci 23
35742871   Curated Info

18

You Y, et al. (2022) Alzheimer's disease associated AKAP9 I2558M mutation alters posttranslational modification and interactome of tau and cellular functions in CRISPR-edited human neuronal cells. Aging Cell, e13617
35567427   Curated Info

19

Zhang S, et al. (2022) Degradation and inhibition of epigenetic regulatory protein BRD4 exacerbate Alzheimer's disease-related neuropathology in cell models. J Biol Chem 298, 101794
35248531   Curated Info

20

Gu L, et al. (2022) Inhibitory Effects of Macelignan on Tau Phosphorylation and Aβ Aggregation in the Cell Model of Alzheimer's Disease. Front Nutr 9, 892558
35662922   Curated Info

21

Lopez-Toledo G, et al. (2022) Patient-Derived Fibroblasts With Presenilin-1 Mutations, That Model Aspects of Alzheimer's Disease Pathology, Constitute a Potential Object for Early Diagnosis. Front Aging Neurosci 14, 921573
35847683   Curated Info

22

Stathas S, et al. (2021) Tau phosphorylation sites serine202 and serine396 are differently altered in chronic traumatic encephalopathy and Alzheimer's disease. Alzheimers Dement
34854540   Curated Info

23

Pan B, et al. (2021) Mechanism by Which Aluminum Regulates the Abnormal Phosphorylation of the Tau Protein in Different Cell Lines. ACS Omega 6, 31782-31796
34870001   Curated Info

24

Dai B, et al. (2021) Myricetin slows liquid-liquid phase separation of Tau and activates ATG5-dependent autophagy to suppress Tau toxicity. J Biol Chem, 101222
34560101   Curated Info

25

Wang XX, et al. (2021) Synthesis and biological evaluation of selective histone deacetylase 6 inhibitors as multifunctional agents against Alzheimer's disease. Eur J Med Chem 225, 113821
34517222   Curated Info

26

Ismael S, Sindi G, Colvin RA, Lee D (2021) Activity-dependent release of phosphorylated human tau from Drosophila neurons in primary culture. J Biol Chem 297, 101108
34473990   Curated Info

27

Samimi N, et al. (2021) Distinct phosphorylation profiles of tau in brains of patients with different tauopathies. Neurobiol Aging 108, 72-79
34536819   Curated Info

28

Bowles KR, et al. (2021) ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids. Cell 184, 4547-4563.e17
34314701   Curated Info

29

Yao H, et al. (2021) Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease. J Med Chem 64, 7483-7506
34024109   Curated Info

30

Elahi M, et al. (2021) High-fat diet-induced activation of SGK1 promotes Alzheimer's disease-associated tau pathology. Hum Mol Genet 30
33890983   Curated Info

31

Cook B, et al. (2021) The small molecule DIPQUO promotes osteogenic differentiation via inhibition of glycogen synthase kinase 3 β signaling. J Biol Chem, 100696
33895139   Curated Info

32

Bi D, et al. (2021) Alginate-Derived Mannuronate Oligosaccharide Attenuates Tauopathy through Enhancing Autophagy. J Agric Food Chem 69, 4438-4445
33829789   Curated Info

33

Carlomagno Y, et al. (2021) The AD tau core spontaneously self-assembles and recruits full-length tau to filaments. Cell Rep 34, 108843
33730588   Curated Info

34

Qi Z, et al. (2021) DHCR24 Knockdown Lead to Hyperphosphorylation of Tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites by Membrane Lipid-Raft Dependent PP2A Signaling in SH-SY5Y Cells. Neurochem Res
33710538   Curated Info

35

Noël A, Foveau B, LeBlanc AC (2021) Caspase-6-cleaved Tau fails to induce Tau hyperphosphorylation and aggregation, neurodegeneration, glial inflammation, and cognitive deficits. Cell Death Dis 12, 227
33649324   Curated Info

36

Bai X, et al. (2021) DHCR24 Knock-Down Induced Tau Hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, Ser396 Epitopes and Inhibition of Autophagy by Overactivation of GSK3β/mTOR Signaling. Front Aging Neurosci 13, 513605
33967735   Curated Info

37

Cantrelle FX, et al. (2021) Phosphorylation and -GlcNAcylation of the PHF-1 Epitope of Tau Protein Induce Local Conformational Changes of the C-Terminus and Modulate Tau Self-Assembly Into Fibrillar Aggregates. Front Mol Neurosci 14, 661368
34220449   Curated Info

38

Shimonaka S, et al. (2020) Asparagine residue 368 is involved in Alzheimer's disease tau strain-specific aggregation. J Biol Chem
32759167   Curated Info

39

Arakhamia T, et al. (2020) Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains. Cell 180, 633-644.e12
32032505   Curated Info

40

Qin M, et al. (2019) SET SUMOylation promotes its cytoplasmic retention and induces tau pathology and cognitive impairments. Acta Neuropathol Commun 7, 21
30767764   Curated Info

41

Li J, Chen W, Yi Y, Tong Q (2018) miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3β in Alzheimer's disease. J Cell Biochem 120
30556160   Curated Info

42

Park J, et al. (2018) A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer's disease. Nat Neurosci 21, 941-951
29950669   Curated Info

43

Zhang Q, et al. (2018) CK2 Phosphorylating I/SET Mediates Tau Pathology and Cognitive Impairment. Front Mol Neurosci 11, 146
29760653   Curated Info

44

Le Pichon CE, et al. (2017) Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease. Sci Transl Med 9
28814543   Curated Info

45

Myeku N, et al. (2016) Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. Nat Med 22, 46-53
26692334   Curated Info

46

Jin N, et al. (2015) Truncation and Activation of Dual Specificity Tyrosine Phosphorylation-regulated Kinase 1A by Calpain I: A MOLECULAR MECHANISM LINKED TO TAU PATHOLOGY IN ALZHEIMER DISEASE. J Biol Chem 290, 15219-37
25918155   Curated Info

47

Day RJ, et al. (2015) Caspase-Cleaved Tau Co-Localizes with Early Tangle Markers in the Human Vascular Dementia Brain. PLoS One 10, e0132637
26161867   Curated Info

48

Luo HB, et al. (2014) SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination. Proc Natl Acad Sci U S A 111, 16586-91
25378699   Curated Info

49

Mondragón-Rodríguez S, et al. (2014) Phosphorylation of tau protein at sites Ser(396-404) is one of the earliest events in Alzheimer's disease and Down syndrome. Neuropathol Appl Neurobiol 40, 121-35
24033439   Curated Info

50

Bailey RM, et al. (2013) LRRK2 phosphorylates novel tau epitopes and promotes tauopathy. Acta Neuropathol 126, 809-27
24113872   Curated Info

51

Yanamandra K, et al. (2013) Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80, 402-14
24075978   Curated Info

52

Yu G, et al. (2013) Ser9 phosphorylation causes cytoplasmic detention of I2PP2A/SET in Alzheimer disease. Neurobiol Aging 34, 1748-58
23374587   Curated Info

53

Luo Y, et al. (2013) PTPA activates protein phosphatase-2A through reducing its phosphorylation at tyrosine-307 with upregulation of protein tyrosine phosphatase 1B. Biochim Biophys Acta 1833, 1235-43
23428800   Curated Info

54

Duka V, et al. (2013) Identification of the sites of tau hyperphosphorylation and activation of tau kinases in synucleinopathies and Alzheimer's diseases. PLoS One 8, e75025
24073234   Curated Info

55

Chu J, Lauretti E, Di Meco A, Praticò D (2013) FLAP pharmacological blockade modulates metabolism of endogenous tau in vivo . Transl Psychiatry 3, e333
24301651   Curated Info

56

Tak H, et al. (2013) Bimolecular fluorescence complementation; lighting-up tau-tau interaction in living cells. PLoS One 8, e81682
24312574   Curated Info

57

Rudrabhatla P, Jaffe H, Pant HC (2011) Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs. FASEB J 25, 3896-905
21828286   Curated Info

58

Jinwal UK, et al. (2011) The Hsp90 kinase co-chaperone Cdc37 regulates tau stability and phosphorylation dynamics. J Biol Chem 286, 16976-83
21367866   Curated Info

59

Yuzwa SA, et al. (2011) Mapping O-GlcNAc modification sites on tau and generation of a site-specific O-GlcNAc tau antibody. Amino Acids 40, 857-68
20706749   Curated Info

60

Thornton C, et al. (2011) AMP-activated protein kinase (AMPK) is a tau kinase, activated in response to amyloid β-peptide exposure. Biochem J 434, 503-12
21204788   Curated Info

61

Leroy A, et al. (2010) Spectroscopic studies of GSK3{beta} phosphorylation of the neuronal tau protein and its interaction with the N-terminal domain of apolipoprotein E. J Biol Chem 285, 33435-44
20679343   Curated Info

62

Alonso AD, et al. (2010) Phosphorylation of tau at Thr212, Thr231, and Ser262 combined causes neurodegeneration. J Biol Chem 285, 30851-60
20663882   Curated Info

63

Bertrand J, Plouffe V, Sénéchal P, Leclerc N (2010) The pattern of human tau phosphorylation is the result of priming and feedback events in primary hippocampal neurons. Neuroscience 168, 323-34
20394726   Curated Info

64

Qian W, et al. (2010) PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3beta. J Alzheimers Dis 19, 1221-9
20308788   Curated Info

65

Buescher JL, Phiel CJ (2010) A noncatalytic domain of glycogen synthase kinase-3 (GSK-3) is essential for activity. J Biol Chem 285, 7957-63
20080974   Curated Info

66

Tremblay MA, Acker CM, Davies P (2010) Tau phosphorylated at tyrosine 394 is found in Alzheimer's disease tangles and can be a product of the Abl-related kinase, Arg. J Alzheimers Dis 19, 721-33
20110615   Curated Info

67

Liu Y, et al. (2009) Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer's disease. J Neurochem 111, 242-9
19659459   Curated Info

68

Liu F, et al. (2009) Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease. Brain 132, 1820-32
19451179   Curated Info

69

Lau KF, et al. (2008) Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription. J Biol Chem 283, 34728-37
18922798   Curated Info

70

Jeganathan S, et al. (2008) Proline-directed pseudo-phosphorylation at AT8 and PHF1 epitopes induces a compaction of the paperclip folding of Tau and generates a pathological (MC-1) conformation. J Biol Chem 283, 32066-76
18725412   Curated Info

71

Wray S, Saxton M, Anderton BH, Hanger DP (2008) Direct analysis of tau from PSP brain identifies new phosphorylation sites and a major fragment of N-terminally cleaved tau containing four microtubule-binding repeats. J Neurochem 105, 2343-52
18315566   Curated Info

72

Terwel D, et al. (2008) Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. Am J Pathol 172, 786-98
18258852   Curated Info

73

Cheng TS, et al. (2008) Glycogen Synthase Kinase 3 Interacts with and Phosphorylates the Spindle-associated Protein Astrin. J Biol Chem 283, 2454-2464
18055457   Curated Info

74

Meske V, Albert F, Ohm TG (2008) Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2A- and glycogen synthase kinase-3 -dependent phosphorylation of Tau. J Biol Chem 283, 100-9
17971449   Curated Info

75

Liu F, et al. (2007) Site-specific effects of tau phosphorylation on its microtubule assembly activity and self-aggregation. Eur J Neurosci 26, 3429-36
18052981   Curated Info

76

Hanger DP, et al. (2007) Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J Biol Chem 282, 23645-54
17562708   Curated Info

77

Yoshiyama Y, et al. (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337-51
17270732   Curated Info

78

Iliev AI, Ganesan S, Bunt G, Wouters FS (2006) Removal of pattern-breaking sequences in microtubule binding repeats produces instantaneous tau aggregation and toxicity. J Biol Chem 281, 37195-204
17008320   Curated Info

79

Liu F, et al. (2006) PKA modulates GSK-3beta- and cdk5-catalyzed phosphorylation of tau in site- and kinase-specific manners. FEBS Lett 580, 6269-74
17078951   Curated Info

80

King TD, Gandy JC, Bijur GN (2006) The protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation and increases sarcoplasmic/endoplasmic reticulum calcium ATPase 2 levels. Exp Cell Res 312, 3693-700
16987514   Curated Info

81

d'Abramo C, Ricciarelli R, Pronzato MA, Davies P (2006) Troglitazone, a peroxisome proliferator-activated receptor-gamma agonist, decreases tau phosphorylation in CHOtau4R cells. J Neurochem 98, 1068-77
16787414   Curated Info

82

Schindowski K, et al. (2006) Alzheimer's disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits. Am J Pathol 169, 599-616
16877359   Curated Info

83

Ding H, Matthews TA, Johnson GV (2006) Site-specific phosphorylation and caspase cleavage differentially impact tau-microtubule interactions and tau aggregation. J Biol Chem 281, 19107-14
16687396   Curated Info

84

Zhang X, et al. (2006) Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules. FASEB J 20, 1272-4
16645045   Curated Info

85

Tatebayashi Y, et al. (2006) c-jun N-terminal kinase hyperphosphorylates R406W tau at the PHF-1 site during mitosis. FASEB J 20, 762-4
16478768   Curated Info

86

Dickey CA, et al. (2006) HSP induction mediates selective clearance of tau phosphorylated at proline-directed Ser/Thr sites but not KXGS (MARK) sites. FASEB J 20, 753-5
16464956   Curated Info

87

Gómez-Ramos A, et al. (2006) Sodium tungstate decreases the phosphorylation of tau through GSK3 inactivation. J Neurosci Res 83, 264-73
16397900   Curated Info

88

Puig B, Rey MJ, Ferrer I (2005) Individual and regional variations of phospho-tau species in progressive supranuclear palsy. Acta Neuropathol (Berl) 110, 261-8
15973541   Curated Info

89

DeGiorgis JA, et al. (2005) Phosphoproteomic analysis of synaptosomes from human cerebral cortex. J Proteome Res 4, 306-15
15822905   Curated Info

90

Arai T, Guo JP, McGeer PL (2005) Proteolysis of non-phosphorylated and phosphorylated tau by thrombin. J Biol Chem 280, 5145-53
15542598   Curated Info

91

Pérez M, et al. (2005) Characterization of a double (amyloid precursor protein-tau) transgenic: tau phosphorylation and aggregation. Neuroscience 130, 339-47
15664690   Curated Info

92

Alonso Adel C, et al. (2004) Promotion of hyperphosphorylation by frontotemporal dementia tau mutations. J Biol Chem 279, 34873-81
15190058   Curated Info

93

Liu F, et al. (2004) O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease. Proc Natl Acad Sci U S A 101, 10804-9
15249677   Curated Info

94

Li G, Yin H, Kuret J (2004) Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J Biol Chem 279, 15938-45
14761950   Curated Info

95

Noble W, et al. (2003) Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 38, 555-65
12765608   Curated Info

96

Grace EA, Busciglio J (2003) Aberrant activation of focal adhesion proteins mediates fibrillar amyloid beta-induced neuronal dystrophy. J Neurosci 23, 493-502
12533609   Curated Info

97

Giasson BI, et al. (2002) The environmental toxin arsenite induces tau hyperphosphorylation. Biochemistry 41, 15376-87
12484777   Curated Info

98

DeTure M, Ko LW, Easson C, Yen SH (2002) Tau assembly in inducible transfectants expressing wild-type or FTDP-17 tau. Am J Pathol 161, 1711-22
12414518   Curated Info

99

Liu F, Iqbal K, Grundke-Iqbal I, Gong CX (2002) Involvement of aberrant glycosylation in phosphorylation of tau by cdk5 and GSK-3beta. FEBS Lett 530, 209-14
12387894   Curated Info

100

Hu YY, et al. (2002) Levels of nonphosphorylated and phosphorylated tau in cerebrospinal fluid of Alzheimer's disease patients : an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay. Am J Pathol 160, 1269-78
11943712   Curated Info

101

Abraha A, et al. (2000) C-terminal inhibition of tau assembly in vitro and in Alzheimer's disease. J Cell Sci 113 Pt 21, 3737-45
11034902   Curated Info

102

Evans DB, et al. (2000) Tau phosphorylation at serine 396 and serine 404 by human recombinant tau protein kinase II inhibits tau's ability to promote microtubule assembly. J Biol Chem 275, 24977-83
10818091   Curated Info

103

Jenkins SM, Zinnerman M, Garner C, Johnson GV (2000) Modulation of tau phosphorylation and intracellular localization by cellular stress. Biochem J 345 Pt 2, 263-70
10620503   Curated Info

104

Schneider A, et al. (1999) Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry 38, 3549-58
10090741   Curated Info

105

Hanger DP, et al. (1998) New phosphorylation sites identified in hyperphosphorylated tau (paired helical filament-tau) from Alzheimer's disease brain using nanoelectrospray mass spectrometry. J Neurochem 71, 2465-76
9832145   Curated Info

106

Preuss U, Mandelkow EM (1998) Mitotic phosphorylation of tau protein in neuronal cell lines resembles phosphorylation in Alzheimer's disease. Eur J Cell Biol 76, 176-84
9716264   Curated Info

107

Illenberger S, et al. (1998) The endogenous and cell cycle-dependent phosphorylation of tau protein in living cells: implications for Alzheimer's disease. Mol Biol Cell 9, 1495-512
9614189   Curated Info

108

Singh TJ, et al. (1997) Protein kinase C and calcium/calmodulin-dependent protein kinase II phosphorylate three-repeat and four-repeat tau isoforms at different rates. Mol Cell Biochem 168, 141-8
9062903   Curated Info

109

Mawal-Dewan M, et al. (1996) Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex. J Neuropathol Exp Neurol 55, 1051-9
8858002   Curated Info

110

Bramblett GT, et al. (1993) Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron 10, 1089-99
8318230   Curated Info