Thr181
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Home > Phosphorylation Site Page: > Thr181  -  Tau iso8 (human)

Site Information
ktPPAPktPPssGEP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447932

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 17 , 32 , 33 ) , flow cytometry ( 10 ) , immunoassay ( 10 ) , mass spectrometry ( 6 , 8 , 12 , 32 ) , microscopy-colocalization with upstream kinase ( 27 ) , mutation of modification site ( 17 , 29 ) , peptide sequencing ( 26 ) , phospho-antibody ( 2 , 3 , 5 , 7 , 8 , 11 , 13 , 14 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 27 , 29 , 30 , 34 ) , western blotting ( 2 , 3 , 4 , 5 , 7 , 13 , 14 , 16 , 17 , 18 , 19 , 22 , 23 , 24 , 26 , 27 , 29 , 30 , 32 , 34 )
Disease tissue studied:
Alzheimer's disease ( 4 , 6 , 7 , 11 , 12 , 25 , 27 , 32 ) , brain cancer ( 27 ) , glioma ( 27 ) , neuroblastoma ( 14 , 23 , 29 , 30 , 33 ) , diabetes mellitus ( 7 ) , type 2 diabetes ( 7 ) , PSP ( 8 , 18 )
Relevant cell line - cell type - tissue:
'brain, brainstem' ( 24 ) , 'brain, caudate-putamen' ( 18 ) , 'brain, cerebral cortex' ( 18 , 24 ) , 'brain, embryonic' ( 34 ) , 'brain, striatum' ( 18 ) , 'neuron, cortical'-brain ( 3 , 17 ) , brain ( 2 , 5 , 6 , 7 , 8 , 12 , 19 , 32 , 34 ) , brain [Tau iso8 (human)] ( 13 , 16 ) , cerebrospinal fluid ( 4 , 10 , 11 , 20 , 22 , 25 ) , CHO (fibroblast) [Tau (human), transfection] ( 33 ) , CHO (fibroblast) ( 14 , 26 , 29 ) , COS (fibroblast) ( 17 ) , H4 (glial) ( 27 ) , LAN-5 (neural crest) ( 33 ) , neuron:synaptosome ( 23 ) , SH-SY5Y (neural crest) ( 14 , 30 ) , SK-N-MC (neural crest) ( 23 , 29 )

Upstream Regulation
Regulatory protein:
CDK5R1 (mouse) ( 24 ) , JNK1 (human) ( 26 ) , nAChRA7 (human) ( 23 ) , PKN1 (human) ( 29 ) , Tau iso8 (human) ( 14 , 16 )
Putative in vivo kinases:
CDK5 (human) ( 17 , 24 )
Kinases, in vitro:
CDK5 (human) ( 15 , 17 , 28 ) , DYRK1A (rat) ( 9 ) , ERK1 (human) ( 23 , 33 ) , ERK2 (human) ( 1 , 23 , 33 ) , GSK3B (human) ( 9 , 15 , 28 ) , JNK1 (human) ( 23 ) , JNK2 (human) ( 23 ) , LRRK2 (human) ( 2 )
Treatments:
alpha-BTX ( 23 ) , alpha-conotoxin_MI ( 23 ) , arsenite ( 26 ) , atropine ( 23 ) , beta-amyloid_42 ( 23 ) , cytosine ( 23 ) , doxycycline ( 27 ) , epibatidine ( 23 ) , kenpaullone ( 26 ) , lithium ( 26 ) , mecamylamine ( 23 ) , methyllycaconitine ( 23 ) , MSH ( 23 ) , mutation ( 21 ) , nicotine ( 23 ) , okadaic_acid ( 26 ) , olomoucine ( 26 ) , SB203580 ( 26 ) , seliciclib ( 26 ) , sorbitol ( 30 ) , U0126 ( 26 )

Downstream Regulation
Effects of modification on Tau iso8:
intracellular localization ( 27 ) , molecular association, regulation ( 21 )
Effects of modification on biological processes:
cytoskeletal reorganization ( 19 , 27 )
Induce interaction with:
Tau iso8 (human) ( 21 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 3 , 4 , 6 , 7 , 10 , 11 , 22 , 25 , 32 ) , ALS ( 34 ) , DLB ( 10 ) , type 2 diabetes ( 7 ) , FTLD ( 22 ) , Parkinson's disease ( 34 ) , PSP ( 8 )

References 

1

Qi H, et al. (2016) Characterization of Neuronal Tau Protein as a Target of Extracellular Signal-regulated Kinase. J Biol Chem 291, 7742-53
26858248   Curated Info

2

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

3

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

4

Meredith JE, et al. (2013) Characterization of Novel CSF Tau and ptau Biomarkers for Alzheimer's Disease. PLoS One 8, e76523
24116116   Curated Info

5

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

6

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

7

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

8

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

9

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

10

Nielsen HM, et al. (2007) Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies. Neurology 69, 1569-79
17761554   Curated Info

11

de Jong D, et al. (2007) CSF neurofilament proteins in the differential diagnosis of dementia. J Neurol Neurosurg Psychiatry 78, 936-8
17314187   Curated Info

12

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

13

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

14

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

15

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

16

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

17

Sakaue F, et al. (2005) Phosphorylation of FTDP-17 mutant tau by cyclin-dependent kinase 5 complexed with p35, p25, or p39. J Biol Chem 280, 31522-9
15994305   Curated Info

18

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

19

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

20

Fellgiebel A, et al. (2004) Association of elevated phospho-tau levels with Alzheimer-typical 18F-fluoro-2-deoxy-D-glucose positron emission tomography findings in patients with mild cognitive impairment. Biol Psychiatry 56, 279-83
15312816   Curated Info

21

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

22

Schoonenboom NS, et al. (2004) Amyloid beta(1-42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease. Neurology 62, 1580-4
15136685   Curated Info

23

Wang HY, Li W, Benedetti NJ, Lee DH (2003) Alpha 7 nicotinic acetylcholine receptors mediate beta-amyloid peptide-induced tau protein phosphorylation. J Biol Chem 278, 31547-53
12801934   Curated Info

24

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

25

Schönknecht P, et al. (2003) Levels of total tau and tau protein phosphorylated at threonine 181 in patients with incipient and manifest Alzheimer's disease. Neurosci Lett 339, 172-4
12614922   Curated Info

26

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

27

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

28

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

29

Taniguchi T, et al. (2001) Phosphorylation of tau is regulated by PKN. J Biol Chem 276, 10025-31
11104762   Curated Info

30

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

31

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

32

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

33

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

34

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