p(HGNC:MAPT, pmod(Ph, Ser, 262))

Entity

Name

MAPT

Namespace

hgnc

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

An important class of kinases that phosphorylate Tau at S262 and the other KXGS motifs in the repeat domain are the microtubule-associated protein/microtubule affinity-regulating kinases (MARKs) PubMed:29215007

We therefore phosphorylated full-length Tau by MARK2. The downfield chemical shift of phosphorylated residues (Fig. 4a) is in agreement with previous reports and confirms phosphorylation at S262, S293, S305, S324, S356, and S416 PubMed:29215007

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

3. Putative phosphorylation sites on tau protein and epitopes specific for major tau antibodies. Red color denotes amino acids phosphorylation in AD brain. PubMed:26751493

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

Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). PubMed:23001711

Immunohistochemical analyses using isoform-selective antibodies demonstrated that MARK4 in a phosphorylated form colocalizes with p-tau Ser262 in granulovacuolar degeneration bodies (GVDs) that progressively accumulate in AD. PubMed:11943212

Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. PubMed:22952452

These data suggest that tau hyperphosphorylation at Thr231, Ser262, and Ser396 by DAPK1 renders the cells more resistant to the kinase-induced apoptotic cell death, providing new insights into the tau-involved apoptotic abortion in the course of chronic neurodegeneration. PubMed:23948915

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

hTau-K280Q mutants showed significantly increased phosphorylation on S262 as compared to both hTau-wt and hTau-K280R flies, when normalised to total hTau (K9JA) levels (**p < 0.01, one-way ANOVA, Fig. 4b,c). Mis-expression of pseudo-acetylated K280Q-hTau in the adult fly nervous system potently exacerbated fly locomotion defects and photoreceptor neurodegeneration. PubMed:26940749

Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). PubMed:23001711

Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). PubMed:23001711

These finding highlight that treatment of PrP106-126 in cultured cells does not alter the level of total tau, but induces a reduction of p-tau262. PubMed:22692785

In parallel, phosphorylation of tau at Ser262 in MARK-transfected cells was investigated using a rabbit antibody recognizing phosphorylated Ser262 of tau (AGG5759) and a mouse anti-tau antibody (SC-21796) (Fig. S1a3). Tau was shown to interact with each of the transfected MARK isoforms (Fig. 1) and to be phosphorylated at Ser262 (Fig. 2). Staurosporine, a non-selective kinase inhibitor, significantly inhibited interactions between tau and each of the four MARK isoforms after treatment with 20 lM staurosporine for 1 h (Fig. 1; p = 0.02 for MARK1–, MARK2– and MARK3–tau interactions and p = 3 9 10-6 for MARK4–tau interaction). Treatment with staurosporine also significantly reduced PLA signals for tau phosphorylation at Ser262 (Fig. 2; p = 0.04 for MARK1- and p = 0.02 for MARK2- and MARK3- and p = 1 9 10-5 for MARK4-mediated tau phosphorylation) PubMed:23666762

In parallel, phosphorylation of tau at Ser262 in MARK-transfected cells was investigated using a rabbit antibody recognizing phosphorylated Ser262 of tau (AGG5759) and a mouse anti-tau antibody (SC-21796) (Fig. S1a3). Tau was shown to interact with each of the transfected MARK isoforms (Fig. 1) and to be phosphorylated at Ser262 (Fig. 2). Staurosporine, a non-selective kinase inhibitor, significantly inhibited interactions between tau and each of the four MARK isoforms after treatment with 20 lM staurosporine for 1 h (Fig. 1; p = 0.02 for MARK1–, MARK2– and MARK3–tau interactions and p = 3 9 10-6 for MARK4–tau interaction). Treatment with staurosporine also significantly reduced PLA signals for tau phosphorylation at Ser262 (Fig. 2; p = 0.04 for MARK1- and p = 0.02 for MARK2- and MARK3- and p = 1 9 10-5 for MARK4-mediated tau phosphorylation) PubMed:23666762

Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). PubMed:23001711

As shown in Figure 7a, compared with the vector control, DAPK1, but not DAPK1K42A, increased the phosphorylation of exogenous tau protein in HeLa cells, as detected by Thr231-specific (AT180), Ser262-specific, and Ser396-specific (PHF-13) antibodies that recognize specific tau phosphoepitopes and/or abnormal conformations specific to AD NFT. PubMed:24853415

These data suggest that tau hyperphosphorylation at Thr231, Ser262, and Ser396 by DAPK1 renders the cells more resistant to the kinase-induced apoptotic cell death, providing new insights into the tau-involved apoptotic abortion in the course of chronic neurodegeneration. PubMed:23948915

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

Furthermore, silencing of both MARK1 and MARK2 blocked DAPK-induced tau S262 phosphorylation (Figure 3e). More importantly, a decrease of pS262 tau, but not total tau, was observed in brain extracts derived from DAPK−/− mice, compared with that from DAPK+/+ mice (Figure 3f). These results strongly suggest a role of endogenous DAPK in stimulating the activity of endogenous MARK, which in turn phosphorylates tau in neurons. PubMed:21311567

Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. PubMed:22952452

Furthermore, silencing of both MARK1 and MARK2 blocked DAPK-induced tau S262 phosphorylation (Figure 3e). More importantly, a decrease of pS262 tau, but not total tau, was observed in brain extracts derived from DAPK−/− mice, compared with that from DAPK+/+ mice (Figure 3f). These results strongly suggest a role of endogenous DAPK in stimulating the activity of endogenous MARK, which in turn phosphorylates tau in neurons. PubMed:21311567

While residues Ser-262, Ser-324, and Ser-356 were completely phosphorylated, Ser-293 in the second repeat was only 84% phosphorylated (Table 1). Furthermore, four non-KXGS phosphorylation sites were detected, two within the repeat domain (Ser-305 in R2 and Ser-352 in R4) and two more at the C-terminus (Ser-413 and Ser-416) (Figure 1B,C). Of these, Ser-305 was 66% phosphorylated and Ser-352, Ser-413, and Ser-416 were ∼45−58% phosphorylated (Table 1). Using wild-type MARK2cat at 25 °C and pH 6.8, the same phosphorylation sites were observed. The three primary sites, Ser-262, Ser-324, and Ser-356, were still completely phosphorylated. PubMed:24251416

Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). PubMed:23001711

Immunohistochemical analyses using isoform-selective antibodies demonstrated that MARK4 in a phosphorylated form colocalizes with p-tau Ser262 in granulovacuolar degeneration bodies (GVDs) that progressively accumulate in AD. PubMed:11943212

Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. PubMed:22952452

Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. PubMed:22952452

We first confirmed that expression of an MKI-GFP fusion protein in rat hippocampal neurons effectively attenuated MARK4-mediated phosphorylation of both endogenous tau (Fig. 3A) and transfected human tau at the 12E8 sites (Fig. 3B). Phosphorylation of tau at the PHF-1 site was also reduced by MKI (Fig. 3A). It is possible that the PHF-1 site is also targeted by PAR-1/MARKs in vivo, or that the phosphorylation of tau at the 12E8 sites is a prerequisite for PHF-1 site phosphorylation, as the 12E8 sites were previously shown to be required for tau phosphorylation at other sites PubMed:22156579

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

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

A recent study has demonstrated that activation of AMPKα1 enhances tau phosphorylation, while inhibition reduces tau phosphorylation at Ser-262, an epitope that is increased in early stages of AD, which promotes the autophagic degradation of tau [87] PubMed:29758300

A recent study has demonstrated that activation of AMPKα1 enhances tau phosphorylation, while inhibition reduces tau phosphorylation at Ser-262, an epitope that is increased in early stages of AD, which promotes the autophagic degradation of tau [87] PubMed:29758300

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

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

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

Thus, the dendritic and axonal MAPT are differentially phosphorylated. Based on this observation, we can conclude that the dendritic MAPT degraded by autophagy or proteasomal pathways is phosphorylated mainly at the 12E8 site. PubMed:30145931

Thus, the dendritic and axonal MAPT are differentially phosphorylated. Based on this observation, we can conclude that the dendritic MAPT degraded by autophagy or proteasomal pathways is phosphorylated mainly at the 12E8 site. PubMed:30145931

For example,the phosphorylation of KXGS motifs (particularly Ser262) in the repeat domain of tau by MARK, PKA or CaMKII can reduce the affinity of tau to microtubules PubMed:26631930

We did not observe any increase in the phosphorylation of the tau repeat domain (as seen by the antibody 12E8) after treating the neurons with TauRDΔK oligomers. PubMed:28528849

Probing for phospho-tau with the 12E8 antibody in cell lysates from K18ΔK280 transfected cells reveals that tau phosphorylation is also decreased by CHIP overexpression (Fig. 1). PubMed:25374103

For example,the phosphorylation of KXGS motifs (particularly Ser262) in the repeat domain of tau by MARK, PKA or CaMKII can reduce the affinity of tau to microtubules PubMed:26631930

For example,the phosphorylation of KXGS motifs (particularly Ser262) in the repeat domain of tau by MARK, PKA or CaMKII can reduce the affinity of tau to microtubules PubMed:26631930

The NMR experiments demonstrate that MARK2- phosphorylation of Tau attenuates its binding to F-actin. Consistent with a reduced affinity, MARK2-phosphorylated Tau failed in bundling actin filaments (Fig. 4e) PubMed:29215007

The NMR experiments demonstrate that MARK2- phosphorylation of Tau attenuates its binding to F-actin. Consistent with a reduced affinity, MARK2-phosphorylated Tau failed in bundling actin filaments (Fig. 4e) PubMed:29215007

In addition, attachment of a phosphate group to S262 in the peptide Tau (254–284) decreased the affinity of the peptide for F-actin (Supplementary Fig. 1) and lowered the amount of Tau (254–284)-promoted actin bundles (Fig. 4f) PubMed:29215007

In addition, attachment of a phosphate group to S262 in the peptide Tau (254–284) decreased the affinity of the peptide for F-actin (Supplementary Fig. 1) and lowered the amount of Tau (254–284)-promoted actin bundles (Fig. 4f) PubMed:29215007

3. Putative phosphorylation sites on tau protein and epitopes specific for major tau antibodies. Red color denotes amino acids phosphorylation in AD brain. PubMed:26751493

The lysine-isoleucine-glycineserine motif (KIGS) or lysine-cysteineglycine-serine motif (KCGS) motifs in the repeat domain (S262, S293, S324, S356) can be phosphorylated by MARK, PKA, SAD kinases, CaMKII and p70S6K, which strongly reduces the tau microtubule interactions (36, 74, 96), [note that phosphorylation at these sites also inhibits tau aggregation, illustrating an analogous role for the repeat domain in the physiological and pathological functions of tau (106)]. PubMed:17493042

The lysine-isoleucine-glycineserine motif (KIGS) or lysine-cysteineglycine-serine motif (KCGS) motifs in the repeat domain (S262, S293, S324, S356) can be phosphorylated by MARK, PKA, SAD kinases, CaMKII and p70S6K, which strongly reduces the tau microtubule interactions (36, 74, 96), [note that phosphorylation at these sites also inhibits tau aggregation, illustrating an analogous role for the repeat domain in the physiological and pathological functions of tau (106)]. PubMed:17493042

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

Immunohistochemical analyses using isoform-selective antibodies demonstrated that MARK4 in a phosphorylated form colocalizes with p-tau Ser262 in granulovacuolar degeneration bodies (GVDs) that progressively accumulate in AD. PubMed:11943212

Immunohistochemical analyses using isoform-selective antibodies demonstrated that MARK4 in a phosphorylated form colocalizes with p-tau Ser262 in granulovacuolar degeneration bodies (GVDs) that progressively accumulate in AD. PubMed:11943212

We first confirmed that expression of an MKI-GFP fusion protein in rat hippocampal neurons effectively attenuated MARK4-mediated phosphorylation of both endogenous tau (Fig. 3A) and transfected human tau at the 12E8 sites (Fig. 3B). Phosphorylation of tau at the PHF-1 site was also reduced by MKI (Fig. 3A). It is possible that the PHF-1 site is also targeted by PAR-1/MARKs in vivo, or that the phosphorylation of tau at the 12E8 sites is a prerequisite for PHF-1 site phosphorylation, as the 12E8 sites were previously shown to be required for tau phosphorylation at other sites PubMed:22156579

These data suggest that tau hyperphosphorylation at Thr231, Ser262, and Ser396 by DAPK1 renders the cells more resistant to the kinase-induced apoptotic cell death, providing new insights into the tau-involved apoptotic abortion in the course of chronic neurodegeneration. PubMed:23948915

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

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

Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. PubMed:22952452

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

A recent study has demonstrated that activation of AMPKα1 enhances tau phosphorylation, while inhibition reduces tau phosphorylation at Ser-262, an epitope that is increased in early stages of AD, which promotes the autophagic degradation of tau [87] PubMed:29758300

A recent study has demonstrated that activation of AMPKα1 enhances tau phosphorylation, while inhibition reduces tau phosphorylation at Ser-262, an epitope that is increased in early stages of AD, which promotes the autophagic degradation of tau [87] PubMed:29758300

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

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

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

Probing for phospho-tau with the 12E8 antibody in cell lysates from K18ΔK280 transfected cells reveals that tau phosphorylation is also decreased by CHIP overexpression (Fig. 1). PubMed:25374103

For example,the phosphorylation of KXGS motifs (particularly Ser262) in the repeat domain of tau by MARK, PKA or CaMKII can reduce the affinity of tau to microtubules PubMed:26631930