Glycogen Synthase Kinase-3β Is Complexed with Tau Protein in Brain Microtubules

Sun, Wei; Qureshi, Hamid Y.; Cafferty, Patrick; Sobue, Kazuya; Agarwal-Mawal, Alka; Neufield, Katherine D.; Paudel, Hemant K.

doi:10.1074/jbc.m107182200

Cited by 110 publications

(113 citation statements)

References 51 publications

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“…Microtubule Sedimentation Assay-Microtubule sedimentation assay was performed as described previously (50). Transfected HEK-293 cells were lysed in PIPES buffer (0.1 M PIPES, 1 mM EGTA, 1 mM MgSO 4 , and 1 mM ␤-mercaptoethanol, 0.2% Nonidet P-40 containing the protease inhibitor mixture).…”

Section: Methodsmentioning

confidence: 99%

Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro

Qureshi¹,

Paudel

2011

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro

Qureshi¹,

Paudel

2011

Journal of Biological Chemistry

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“…Dishevelled activates JNK (36), as does PSK (2), but the effects of PSK on glycogen synthase kinase-3␤ are unknown. PSK does bind directly to MTs in vitro, whereas glycogen synthase kinase-3␤ has been shown to bind MTs indirectly via its association with the neuronal MAP tau, and JNK may interact with MTs via JNK-interacting proteins (37,38).…”

Section: Psk Localizes To Mts Via Its C Terminus and Alters Mt Organimentioning

confidence: 99%

The Prostate-derived Sterile 20-like Kinase (PSK) Regulates Microtubule Organization and Stability

Mitsopoulos¹,

Zihni²,

Garg

et al. 2003

Journal of Biological Chemistry

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Sterile 20 (STE20) protein kinases, which include germinal center kinases and p21-activated protein kinases, are known to activate mitogen-activated protein kinase pathways (c-Jun NH 2 -terminal kinase, p38, or extracellular signal-regulated kinase), leading to changes in gene transcription. Some STE20s can also regulate the cytoskeleton, and we have shown that the germinal center kinase-like kinase prostate-derived STE20-like kinase (PSK) affects actin cytoskeletal organization. Here, we demonstrate that PSK colocalizes with microtubules; and that this localization is disrupted by the microtubule depolymerizing agent nocodazole. The association of PSK with microtubules results in the production of stabilized perinuclear microtubule cables that are nocodazole-resistant and contain increased levels of acetylated ␣-tubulin. Recent work has demonstrated that some STE20s can also regulate the cell cytoskeleton. PAKs interact with Rac or Cdc42 GTPases via the CRIB domain and act as downstream effectors for these small GTP binding proteins to regulate the actin cytoskeleton (reviewed in Refs. 4, 5). Rac and Cdc42 stimulated morphological rearrangements are blocked by mutated PAK, and activated PAK down-regulates actin stress fibers and focal complexes (6 -8). Some of the effects of PAK1 can be attributed to the phosphorylation of downstream kinases, such as myosin light chain kinase, which reduces its activity toward myosin light chain, and LIM kinase 1, which phosphorylates and inactivates the actin depolymerizing protein cofilin to generate actin clusters (9, 10). X-PAK5 co-localizes to actin and microtubules (MTs) and produces stabilized MTs that are associated in bundles, and PAK1 accumulates at the MT-organizing center and along mitotic spindles during mitosis (11,12).Although GCK-like STE20s lack a CRIB domain, recent work has demonstrated that members of this subfamily of STE20s can also regulate the actin cytoskeleton. Proline-and alanine-rich STE20-related kinase associates with actin, and prostate-derived STE20-like kinase (PSK), Traf2-and Nckinteracting kinase, and STE20-like kinase (SLK) decrease actin stress fibers and focal adhesions and inhibit cell spreading (3,(13)(14)(15). SLK has recently been shown to associate with MTs at the cell periphery (16).There is increasing evidence that actin filaments and MTs are coordinately regulated during the establishment and maintenance of cell polarity, division, and motility. The ability of MTs to undergo transitions between growth, shrinkage and pause are crucial for their function and the regulation of these processes. MT dynamics and stability are controlled by multiple factors, which include MT-associated proteins (MAPs), MTaffinity regulated kinases, severing factors (e.g. katanin), and catastrophe proteins (e.g. stathmin/OP18 and XKCM1) (reviewed in (17)). MAPs provide a focal point for MT regulation and act as structural proteins that lack enzymatic activity but promote the assembly of tubulin and MT stability. The affinity of MAPs for MTs is controlled by...

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“…Specially, we measured the activated forms of cdk5, GSK-3␤, p38 -MAPK, and JNK because these kinases are known to phosphorylate tau in vitro and in vivo (Atzori et al, 2001;Savage et al, 2002;Sun et al, 2002;Liu et al, 2003). Among them, the activities of GSK-3␤, p38 -MAPK, and JNK are all regulated via phosphorylation at specific amino acids.…”

Section: Lps-induced Inflammation Exacerbates Tau Pathology Via Cdk5mentioning

confidence: 99%

Lipopolysaccharide-Induced Inflammation Exacerbates Tau Pathology by a Cyclin-Dependent Kinase 5-Mediated Pathway in a Transgenic Model of Alzheimer's Disease

Kitazawa¹,

Oddo²,

Yamasaki³

et al. 2005

J. Neurosci.

604

448

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Inflammation is a critical component of the pathogenesis of Alzheimer's disease (AD).Although not an initiator of this disorder, inflammation nonetheless plays a pivotal role as a driving force that can modulate the neuropathology. Here, we characterized the time course of microglia activation in the brains of a transgenic model of AD (3xTg-AD) and discerned its relationship to the plaque and tangle pathology. We find that microglia became activated in a progressive and age-dependent manner, and this activation correlated with the onset of fibrillar amyloid ␤-peptide plaque accumulation and tau hyperphosphorylation. To determine whether microglial activation can exacerbate the pathology, we exposed young 3xTg-AD mice to lipopolysaccharide (LPS), a known inducer of CNS inflammation. Although amyloid precursor protein processing appeared unaffected, we find that LPS significantly induced tau hyperphosphorylation at specific sites that were mediated by the activation of cyclin-dependent kinase 5 (cdk5) through increased formation of the p25 fragment. We further show that administration of roscovitine, a selective and potent inhibitor of cdk5, markedly blocked the LPS-induced tau phosphorylation in the hippocampus. Therefore, this study clearly demonstrates that microglial activation exacerbates key neuropathological features such as tangle formation.

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Glycogen Synthase Kinase-3β Is Complexed with Tau Protein in Brain Microtubules

Cited by 110 publications

References 51 publications

Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro

Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro

The Prostate-derived Sterile 20-like Kinase (PSK) Regulates Microtubule Organization and Stability

Lipopolysaccharide-Induced Inflammation Exacerbates Tau Pathology by a Cyclin-Dependent Kinase 5-Mediated Pathway in a Transgenic Model of Alzheimer's Disease

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