1. Catalog
  2. Nodes
  3. p(HGNC:MAPT, pmod(Ph, Ser, 202))

p(HGNC:MAPT, pmod(Ph, Ser, 202))

Equivalencies: 2 | Classes: 2 | Children: 0 | Explore

Entity

Name
MAPT
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 13

Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent kinases cdk2 and cdk5 v1.0.0

Identification of the Tau phosphorylation pattern that drives its aggregation v1.0.0

Neuropathogenic role of adenylate kinase-1 in Aβ-mediated tau phosphorylation via AMPK and GSK3β. v1.0.0

Tau oligomers and tau toxicity in neurodegenerative disease v1.0.0

Tau oligomers and tau toxicity in neurodegenerative disease by Ward et al., 2012

TAU and Interaction Partners v1.2.5

TAU Interactions Section of NESTOR

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Anatabine Attenuates Tau Phosphorylation and Oligomerization in P301S Tau Transgenic Mice v1.0.0

PP2A and Alzheimer Disease v1.0.0

Pathological missorting of endogenous MAPT/Tau in neurons caused by failure of protein degradation systems v1.0.0

Extracellular low-n oligomers of tau cause selective synaptotoxicity without affecting cell viability v1.0.0

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation* v1.0.0

Caenorhabditis elegans models of tauopathy v1.0.0

Alzheimer's disease pathological lesions activate the spleen tyrosine kinase. v1.0.0

In-Edges 45

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(FPLX:ERK) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(FPLX:GSK3) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK2) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

The diagnostic antibodies AT8, TAU-1, SM131, SM134, and SM133 react to phosphorylation similarly as with MAPK and GSK-3, indicating that SP motifs before the repeat region (S199 and/or S202, S235) and after the repeats (S396, S404) become phosphorylated (Fig. 2,-2,); note that AT8, SMUl, and SM134 react with PHFs where the epitopes containing SP motifs are phosphorylated, while TAU-1 and SM133 react with normal tau where the epitopes are not phosphorylated PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK2) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:MAPT) hasVariant p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Appears in Networks:

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

In both the detergent soluble and insoluble fractions of the brain and spinal cord homogenates of Tg Tau P301S mice, we found that tau phosphorylation was significantly reduced (T-tests, P<0.05) by the anatabine treatment for all the AD phosphorylated epitopes tested (Figure 6) DOI:10.4172/2168-975X.1000126

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Spinal Cord

act(p(HGNC:MAPK1)) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

When combined with ERK2 catalyzed phosphorylation, the turn-like disrupting G207V mutation in TauF8 hence leads to fast aggregation that already occurs during the phosphorylation reaction. PubMed:28784767

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736

Appears in Networks:

p(HGNC:GSK3B) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Glycogen synthase 3β (GSK3β) is one of the main serine-threonine kinase responsible for tau phosphorylation and has been shown to affect tau phosphorylation at multiple AD relevant epitopes including Ser396, Ser404, Thr231 and Ser202 DOI:10.4172/2168-975X.1000126

Appears in Networks:

a(HBP:"Tau aggregates") association p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

TNT1 also co-localizes in tissue with the phospho-epitope defined by the AT8 antibody, indicating that PAD exposure represents an early event in AD pathology PubMed:22817713

Appears in Networks:
Annotations
Confidence
High
MeSH
Intracellular Space

a(HBP:"Tau oligomers") association p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

TNT1 also co-localizes in tissue with the phospho-epitope defined by the AT8 antibody, indicating that PAD exposure represents an early event in AD pathology PubMed:22817713

Appears in Networks:
Annotations
Confidence
High
MeSH
Intracellular Space

p(HGNC:CDC37) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Quantification of the Western blot showed that Cdc37 knockdown reduced phospho-Thr-231, phospho-Ser-199/Ser-202, phospho-Ser-396/Ser-404, and phospho-Ser-262/Ser-356 tau. PubMed:21367866

Appears in Networks:

complex(p(HGNC:FKBP5), p(HGNC:MAPT)) association p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

Appears in Networks:

p(HGNC:FKBP5) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

Appears in Networks:

p(HGNC:GSK3B) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

These data indicated that phosphorylation of PP2A dephosphorylation sites is an important recognition signal for ubiquitination. We used 200 μg of amino-terminal His-tagged full-length recombinant human tau in an in vitro phosphorylation reaction with GSK-3Beta. When phosphorylated, the tau protein reacted on immunoblots with PHF1 (25, 26) and AT8 (24), indicating that at least sites Ser202, Thr205, Ser396, and Ser404 were phosphorylated. Following GSK-3Beta incubation, this tau served as an excellent substrate for in vitro ubiquitination using UbcH5B and the cofactor fraction from AD tau immunoprecipitates (Fig. 2a). This finding suggested that GSK-3Beta can place phosphates on tau that create recognition sites for an E3 Ub ligase. PubMed:14612456

Appears in Networks:

a(CHEBI:"okadaic acid") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Both brain proteins were preferentially modified by SUMO1, as compared with SUMO2 or SUMO3. Tau contains two SUMO consensus sequences with Lys(340) as the major sumoylation site. Although both tau and alpha-synuclein are targets for proteasomal degradation, only tau sumoylation was affected by inhibitors of the proteasome pathway. Treatment with the phosphatase inhibitor, okadaic acid, or the microtubule depolymerizing drug, colchicine, up-regulated tau sumoylation. PubMed:16464864

Appears in Networks:

a(CHEBI:Nilvadipine) decreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Western blot analyses of brain homogenates show that (−)-nilvadipine significantly reduces Tau phosphorylation in AT8 (phosphorylated Ser-199/Ser-202/Thr-205) and PHF-1 (phosphorylated Ser-396/Ser-404) epitopes PubMed:25331948

Appears in Networks:

a(GO:"neurofibrillary tangle") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

E391-3610 mice (higher expressers) exhibit robust somatodendritic distribution of phospho- Ser 202/Thr 205 tau throughout the cortex, in hippocampal CA3 pyramidal neurons, CA1 apical dendrites and cell bodies and dentate granule cells. PubMed:22002427

Appears in Networks:
Annotations
Uberon
CA1 field of hippocampus
Uberon
CA3 field of hippocampus
Uberon
cerebral cortex
Uberon
dentate gyrus granule cell layer

a(HBP:"Tau epitope, CP13") equivalentTo p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Appears in Networks:

m(MIRBASE:"rno-mir-195") negativeCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. PubMed:26118667

Appears in Networks:

complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Ser, 202))) hasComponent p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 280)) decreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Surprisingly, we show that tau acetylation alters phosphorylation at residues S202/T205 (comprising the AT8 epitope), indicating acetylation-dephosphorylation cross-talk. Using a series of biochemical approaches, we found that K280/K281 acetylation impaired tau-mediated MT assembly function and also significantly enhanced tau aggregation. We also demonstrate that methylene blue, a reported tau aggregation inhibitor, modulates tau acetylation, a novel mechanism of action for this class of compounds PubMed:28287136

Appears in Networks:

p(FPLX:PKA) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

p(HBP:"Tau epitope, CP13") equivalentTo p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Appears in Networks:

act(p(HGNC:GSK3B), ma(kin)) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:GSK3B)) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Filamentous, but not soluble, forms of wild-type tau inhibit anterograde, kinesin-based fast axonal transport (FAT) by activating axonal protein phosphatase 1 (PP1) and glycogen synthase kinase 3 (GSK3), independent of microtubule binding. Amino acids 2-18 of tau, comprising a phosphatase-activating domain (PAD), are necessary and sufficient for activation of this pathway. Various pathogenic forms of tau displaying increased exposure of PAD inhibited anterograde FAT in squid axoplasm. Immunohistochemical studies using a novel PAD-specific monoclonal antibody in human postmortem tissue indicated that increased PAD exposure represents an early pathogenic event in AD that closely associates in time with AT8 immunoreactivity. We propose a model of pathogenesis in which disease-associated changes in tau conformation lead to increased exposure of PAD, activation of PP1-GSK3, and inhibition of FAT PubMed:21734277

Appears in Networks:

p(HGNC:MAPK12) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

For AT8, which recognises phosphorylated S202 and T205 in tau, SAPK3/p38gamma gave the strongest labelling PubMed:11943212

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 174)) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

The acetyl-mimicking mutant K174Q slows tau turnover and induces cognitive deficits in vivo. Acetyltransferase p300-induced tau acetylation is inhibited by salsalate and salicylate, which enhance tau turnover and reduce tau levels. In the PS19 transgenic mouse model of FTD, administration of salsalate after disease onset inhibited p300 activity, lowered levels of total tau and tau acetylated at K174, rescued tau-induced memory deficits and prevented hippocampal atrophy. PubMed:26390242

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. PubMed:22833681

Appears in Networks:

p(HGNC:MAPT, pmod(Sumo, Lys, 340)) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Both brain proteins were preferentially modified by SUMO1, as compared with SUMO2 or SUMO3. Tau contains two SUMO consensus sequences with Lys(340) as the major sumoylation site. Although both tau and alpha-synuclein are targets for proteasomal degradation, only tau sumoylation was affected by inhibitors of the proteasome pathway. Treatment with the phosphatase inhibitor, okadaic acid, or the microtubule depolymerizing drug, colchicine, up-regulated tau sumoylation. PubMed:16464864

Appears in Networks:

p(HGNC:MAPT, var("p.Glu391*")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

E391-3610 mice (higher expressers) exhibit robust somatodendritic distribution of phospho- Ser 202/Thr 205 tau throughout the cortex, in hippocampal CA3 pyramidal neurons, CA1 apical dendrites and cell bodies and dentate granule cells. PubMed:22002427

Appears in Networks:
Annotations
Uberon
CA1 field of hippocampus
Uberon
CA3 field of hippocampus
Uberon
cerebral cortex
Uberon
dentate gyrus granule cell layer

p(HGNC:MAPT, var("p.Pro301Leu")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

We studied underlying pathomechanisms in tauopathies using pR5 mice that express the P301L tau mutation found in familial forms of frontotemporal dementia. In a longitudinal study we investigated the functional status of glycogen synthase kinase-3 and correlated it with the appearance of distinct tau phospho-epitopes. Neurons displaying increases in activating phosphorylation of glycogen synthase kinase-3α/β at tyrosine 279/216 also showed an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. PubMed:23294633

Appears in Networks:

p(HGNC:MAPT, var("p.Pro301Ser")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

We developed a transgenic mouse, named TPR50, harboring human P301S tau. Tau phosphorylation in the hippocampus of TPR50 mice increased with age, particularly at S202/T205. Therefore, cognitive dysfunction in TPR50 mice may result from early MT dysfunction and impaired axonal transport rather than accumulation of insoluble tau and neurodegeneration. PubMed:24406748

Appears in Networks:

p(HGNC:TTBK1) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Epitopes S198, S199, S202, T205, S422 (Lund 2013) PubMed:18239272

Appears in Networks:

a(CHEBI:"okadaic acid") increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Similar findings have been observed in metabolically active rat brain slices, where a selective inhibition of PP2A with OA results in an aberrant phosphorylation of tau at the same residues seen in AD brains at serines (Ser) 198, 199, 202, 396, 404, 422 and 262 [11, 47, 48]. PubMed:22299660

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Similar findings have been observed in metabolically active rat brain slices, where a selective inhibition of PP2A with OA results in an aberrant phosphorylation of tau at the same residues seen in AD brains at serines (Ser) 198, 199, 202, 396, 404, 422 and 262 [11, 47, 48]. PubMed:22299660

Appears in Networks:

a(CHEBI:epoxomicin) causesNoChange p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Missorted dendritic MAPT showed phosphorylation mainly at the 12E8 sites upon treatment with either the autophagy inhibitor wortmannin (Fig. 4B; 57.2±9.4% dendrites) or the proteasomal inhibitor epoxomicin (Fig. 4C, 62.9±7.4% dendrites) (Fig. 4A-C, quantification in Fig. 4D), but not at the AT8 and the PHF1 (p-S396/p-S404) sites (Fig. S5, Fig 4D). PubMed:30145931

Appears in Networks:
Annotations
MeSH
Dendrites

a(CHEBI:wortmannin) causesNoChange p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Missorted dendritic MAPT showed phosphorylation mainly at the 12E8 sites upon treatment with either the autophagy inhibitor wortmannin (Fig. 4B; 57.2±9.4% dendrites) or the proteasomal inhibitor epoxomicin (Fig. 4C, 62.9±7.4% dendrites) (Fig. 4A-C, quantification in Fig. 4D), but not at the AT8 and the PHF1 (p-S396/p-S404) sites (Fig. S5, Fig 4D). PubMed:30145931

Appears in Networks:
Annotations
MeSH
Dendrites

a(HBP:"amyloid-beta oligomers") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

In addition, it has been reported that in cultured neurons, Aβ oligomers induce MAPT missorting into the somatodendritic compartment, and the missorted MAPT is phosphorylated mainly at the 12E8 (p-S262/p-S356) and AT8 (p-S202/p-T205) sites [6]. PubMed:30145931

Appears in Networks:
Annotations
MeSH
Dendrites

p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

We also checked the phosphorylation of tau at other sites (e.g., using the antibody AT8, reacting only with the endogenous tau) and did not observe an increase in the phosphorylation. PubMed:28528849

Appears in Networks:

a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide") decreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

We further confirmed that possibility by showing that Tau phosphorylation at the typical GSK3β sites (PHF-1 and CP13) is reduced following treatment of SH-SY5Y cells with BAY61-3606, whereas Tau phosphorylation at the RZ3 site was not significantly impacted in SH-SY5Y cells (Fig. 9C). PubMed:25331948

Appears in Networks:

p(HGNC:GSK3B) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

We further confirmed that possibility by showing that Tau phosphorylation at the typical GSK3β sites (PHF-1 and CP13) is reduced following treatment of SH-SY5Y cells with BAY61-3606, whereas Tau phosphorylation at the RZ3 site was not significantly impacted in SH-SY5Y cells (Fig. 9C). PubMed:25331948

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

For example, both soluble and insoluble tau from transgenic worms generated by Kraemer and colleagues (66) was phosphorylated at most of the sites examined; however, the insoluble tau did not show reactivity at the AT8 and pS422 epitopes, which are pronounced in human AD tau. PubMed:29191965

Appears in Networks:

act(p(HGNC:SYK)) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Altogether, these data suggest that only certain pathogenic forms of tau (MC1, Y18) promote Syk activation, whereas Syk activation appears to directly in- duce tau phosphorylation at Y18 and to indirectly regulate tau phosphorylation at multiple epitopes (S396/404, S202) as well as tau misfolding (MC1, TOC1). PubMed:28877763

Appears in Networks:

Out-Edges 26

p(HGNC:MAPT, pmod(Ph, Ser, 202)) partOf p(HBP:"Tau epitope, AT8") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) association a(HBP:"Tau aggregates") View Subject | View Object

TNT1 also co-localizes in tissue with the phospho-epitope defined by the AT8 antibody, indicating that PAD exposure represents an early event in AD pathology PubMed:22817713

Appears in Networks:
Annotations
Confidence
High
MeSH
Intracellular Space

p(HGNC:MAPT, pmod(Ph, Ser, 202)) association a(HBP:"Tau oligomers") View Subject | View Object

TNT1 also co-localizes in tissue with the phospho-epitope defined by the AT8 antibody, indicating that PAD exposure represents an early event in AD pathology PubMed:22817713

Appears in Networks:
Annotations
Confidence
High
MeSH
Intracellular Space

p(HGNC:MAPT, pmod(Ph, Ser, 202)) isA p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) isA p(RGD:Mapt, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) association complex(p(HGNC:FKBP5), p(HGNC:MAPT)) View Subject | View Object

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(HGNC:FKBP5) View Subject | View Object

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(HGNC:CDC37) View Subject | View Object

Quantification of the Western blot showed that Cdc37 knockdown reduced phospho-Thr-231, phospho-Ser-199/Ser-202, phospho-Ser-396/Ser-404, and phospho-Ser-262/Ser-356 tau. PubMed:21367866

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(FPLX:PKA) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) partOf complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Ser, 202))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) partOf p(HBP:"Tau epitope, AT8") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) equivalentTo a(HBP:"Tau epitope, CP13") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. PubMed:26118667

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) equivalentTo p(HBP:"Tau epitope, CP13") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) View Subject | View Object

Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. PubMed:22833681

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(HGNC:MAPT, var("p.Pro301Ser")) View Subject | View Object

We developed a transgenic mouse, named TPR50, harboring human P301S tau. Tau phosphorylation in the hippocampus of TPR50 mice increased with age, particularly at S202/T205. Therefore, cognitive dysfunction in TPR50 mice may result from early MT dysfunction and impaired axonal transport rather than accumulation of insoluble tau and neurodegeneration. PubMed:24406748

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(HGNC:MAPT, var("p.Pro301Leu")) View Subject | View Object

We studied underlying pathomechanisms in tauopathies using pR5 mice that express the P301L tau mutation found in familial forms of frontotemporal dementia. In a longitudinal study we investigated the functional status of glycogen synthase kinase-3 and correlated it with the appearance of distinct tau phospho-epitopes. Neurons displaying increases in activating phosphorylation of glycogen synthase kinase-3α/β at tyrosine 279/216 also showed an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. PubMed:23294633

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(HGNC:MAPT, var("p.Glu391*")) View Subject | View Object

E391-3610 mice (higher expressers) exhibit robust somatodendritic distribution of phospho- Ser 202/Thr 205 tau throughout the cortex, in hippocampal CA3 pyramidal neurons, CA1 apical dendrites and cell bodies and dentate granule cells. PubMed:22002427

Appears in Networks:
Annotations
Uberon
CA1 field of hippocampus
Uberon
CA3 field of hippocampus
Uberon
cerebral cortex
Uberon
dentate gyrus granule cell layer

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

E391-3610 mice (higher expressers) exhibit robust somatodendritic distribution of phospho- Ser 202/Thr 205 tau throughout the cortex, in hippocampal CA3 pyramidal neurons, CA1 apical dendrites and cell bodies and dentate granule cells. PubMed:22002427

Appears in Networks:
Annotations
Uberon
CA1 field of hippocampus
Uberon
CA3 field of hippocampus
Uberon
cerebral cortex
Uberon
dentate gyrus granule cell layer

p(HGNC:MAPT, pmod(Ph, Ser, 202)) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) partOf a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation a(CHEBI:"okadaic acid") View Subject | View Object

Both brain proteins were preferentially modified by SUMO1, as compared with SUMO2 or SUMO3. Tau contains two SUMO consensus sequences with Lys(340) as the major sumoylation site. Although both tau and alpha-synuclein are targets for proteasomal degradation, only tau sumoylation was affected by inhibitors of the proteasome pathway. Treatment with the phosphatase inhibitor, okadaic acid, or the microtubule depolymerizing drug, colchicine, up-regulated tau sumoylation. PubMed:16464864

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(HGNC:MAPT, pmod(Sumo, Lys, 340)) View Subject | View Object

Both brain proteins were preferentially modified by SUMO1, as compared with SUMO2 or SUMO3. Tau contains two SUMO consensus sequences with Lys(340) as the major sumoylation site. Although both tau and alpha-synuclein are targets for proteasomal degradation, only tau sumoylation was affected by inhibitors of the proteasome pathway. Treatment with the phosphatase inhibitor, okadaic acid, or the microtubule depolymerizing drug, colchicine, up-regulated tau sumoylation. PubMed:16464864

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Similar findings have been observed in metabolically active rat brain slices, where a selective inhibition of PP2A with OA results in an aberrant phosphorylation of tau at the same residues seen in AD brains at serines (Ser) 198, 199, 202, 396, 404, 422 and 262 [11, 47, 48]. PubMed:22299660

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation a(HBP:"amyloid-beta oligomers") View Subject | View Object

In addition, it has been reported that in cultured neurons, Aβ oligomers induce MAPT missorting into the somatodendritic compartment, and the missorted MAPT is phosphorylated mainly at the 12E8 (p-S262/p-S356) and AT8 (p-S202/p-T205) sites [6]. PubMed:30145931

Appears in Networks:
Annotations
MeSH
Dendrites

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

For example, both soluble and insoluble tau from transgenic worms generated by Kraemer and colleagues (66) was phosphorylated at most of the sites examined; however, the insoluble tau did not show reactivity at the AT8 and pS422 epitopes, which are pronounced in human AD tau. PubMed:29191965

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.