Casein Kinase 1 Delta Phosphorylates Tau and Disrupts Its Binding to Microtubules

Li, Guibin; Yin, Haishan; Kuret, Jeff

doi:10.1074/jbc.m314116200

Cited by 136 publications

(117 citation statements)

References 75 publications

(72 reference statements)

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“…As illustrated in Figure 4c, after 6-8 h of incubation with IC261 (see also Materials and methods; Cooper and Lampe (2002) and Li et al (2004)), the signal intensity of nm23 phosphorylation decreased by 65% (quantified by imaging scan analyses; data not shown). To confirm any effects of inhibition of CKI on nm23 phosphorylation in cells and to avoid any misinterpretation relating to the relatively high levels of IC261 used (see below), here we also treated the MDA-MB-H1-177 cells with the two additional CKI inhibitors indicated above: D4476 and CKI-7 (Figure 4d).…”

Section: Resultsmentioning

confidence: 92%

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Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility

Garzia¹,

D’Angelo²,

Amoresano

et al. 2007

Oncogene

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The combination of an increase in the cAMP-phosphodiesterase activity of h-prune and its interaction with nm23-H1 have been shown to be key steps in the induction of cellular motility in breast cancer cells. Here we present the molecular mechanisms of this interaction. The region of the nm23-h-prune interaction lies between S120 and S125 of nm23, where missense mutants show impaired binding; this region has been highly conserved throughout evolution, and can undergo serine phosphorylation by casein kinase I. Thus, the casein kinase I d-e specific inhibitor IC261 impairs the formation of the nm23-hprune complex, which translates 'in vitro' into inhibition of cellular motility in a breast cancer cellular model. A competitive permeable peptide containing the region for phosphorylation by casein kinase I impairs cellular motility to the same extent as IC261. The identification of these two modes of inhibition of formation of the nm23-H1-h-prune protein complex pave the way toward new challenges, including translational studies using IC261 or this competitive peptide 'in vivo' to inhibit cellular motility induced by nm23-H1-h-prune complex formation during progression of breast cancer.

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Section: Resultsmentioning

confidence: 92%

“…In these assays, IC261 was used at a concentration of 50 mM, CKI-7 at 400 mM, and D4476 at 25 mM, according to the concentrations reported in the literature (Cooper and Lampe, 2002;Izeradjene et al, 2004;Li et al, 2004;Rena et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility

Garzia¹,

D’Angelo²,

Amoresano

et al. 2007

Oncogene

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“…In vitro, GSK-3 phosphorylates tau on ~40 Ser/Thr residues, and 348 CK1 is the only other kinase comparable to GSK-3 in that it phosphorylates tau residues in similar numbers [31] . GSK-3 phosphorylation reduces the capability of tau to promote microtubule assembly in vitro and in cells [33,34] . GSK-3 together with the activity of other kinases such as CK1, Cdk5, and MARK, has the ability to signifi cantly affect tau phosphorylation and modulate its neuronal function [35][36][37][38] .…”

Section: Phosphorylation Of Tau Is Mainly Regulated Through Kinases Amentioning

confidence: 99%

Tau-induced neurodegeneration: mechanisms and targets

Beharry

Cohen

et al. 2014

Neurosci. Bull.

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The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau's functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications: hyperphosphorylation, ubiquitination, glycation, glycosylation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifi cations can alter tau's biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and propose a mechanism of neurodegeneration.Keywords: tau; phosphorylation; neurodegeneration; tauopathies; mitochondria; microtubules; tubulin; kinases; phosphatases; Alzheimer's disease ·Review· IntroductionAlzheimer 's disease (AD), first described by Alois Alzheimer more than 100 years ago [1] , is a progressive neurodegenerative disorder, characterized by an insidious onset with irreversible cognitive declines that lead to profound mental deterioration causing dementia [2] . Two major forms of lesion characterize AD: amyloid as diffuse neurotic plaques primarily composed of the Aβ peptide [3] , which are mainly insoluble deposits of protein and cellular material, and neurofibrillary tangles composed of fi lamentous hyperphosphorylated tau protein that builds up inside the neuron [4,5] .Amyloid precursor protein (APP) is a highly conserved transmembrane protein [6] believed to play a role in synapse formation, synaptic plasticity, and neuronal survival [7][8][9] .In AD, APP is cleaved by β-and γ-secretases leading to the overproduction of an abnormal proteolytic byproduct called amyloid beta (Aβ) [10] . Upon cleavage fragments of Aβ of various sizes are released from the membrane and aggregate in the brain to form the characteristic plaques seen in AD. Plaques are composed primarily of the 40 and 42 amino-acid peptide fragments Aβ40 and Aβ42, the latter being the predominant species. In addition, Aβ42 is more prone to aggregation and deposition and therefore the cause of neurotoxicity, as well as synaptic loss [11] .The second lesion in AD is formed by aggregates of the microtubule-associated protein tau, which forms intracytoplasmic neuronal inclusions or neurofibrillary tangles when hyperphosphorylated [12] . Tau is associated with neurons of the central nervous system [13] and its main biological function is promoting the in vitro assembly and stabilization of microtubules in the cytoskeleton [14,15] . Tau is a phosphoprotein that is encoded by a single gene, MAPT, located on chromosome 17q21 [16] ; alternative splicing of the gene produces six major isoforms expressed in the adult human brain [17] . Isoforms derive their names from the number of microtubule-binding repeat s...

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“…As a result, they can function processively or synergize with other protein kinases to support high-stoichiometry substrate phosphorylation [14]. CK1 activity associates with brain microtubules [42] and contributes to basal levels of tau phosphorylation in cultured cells [28]. Moreover, at least one isoform, Ckiδ, can phosphorylate tau and modulate its binding affinity for microtubules when highly overexpressed in cultured cells [28].…”

mentioning

confidence: 99%

“…CK1 activity associates with brain microtubules [42] and contributes to basal levels of tau phosphorylation in cultured cells [28]. Moreover, at least one isoform, Ckiδ, can phosphorylate tau and modulate its binding affinity for microtubules when highly overexpressed in cultured cells [28]. To identify which isoforms gain access to substrates under pathophysiologically relevant conditions, their colocalization with intact AD lesions has been investigated immunohistochemically in diseased tissue.…”

mentioning

confidence: 99%

Casein kinase 1 alpha associates with the tau-bearing lesions of inclusion body myositis

Kannanayakal

Mendell

Kuret

2008

Neuroscience Letters

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Inclusion body myositis and Alzheimer's disease are age-related disorders characterized in part by the appearance of intracellular lesions composed of filamentous aggregates of the microtubuleassociated protein tau. Abnormal tau phosphorylation accompanies tau aggregation and may be an upstream pathological event in both diseases. Enzymes implicated in tau hyperphosphorylation in Alzheimer's disease include members of the casein kinase-1 family of phosphotransferases, a group of structurally related protein kinases that frequently function in tandem with the ubiquitin modification system. To determine whether casein kinase-1 isoforms associate with degenerating muscle fibers of inclusion body myositis, muscle biopsy sections isolated from sporadic disease cases were subjected to double-label fluorescence immunohistochemistry using selective anti-casein kinase 1 and anti-phospho-tau antibodies. Results showed that the alpha isoform of casein kinase 1, but not the delta or epsilon isoforms, stained degenerating muscle fibers in all eight inclusion body myositis cases examined. Staining was almost exclusively localized to phospho-tau bearing inclusions. These findings, which extend the molecular similarities between inclusion body myositis muscle and Alzheimer's disease brain, implicate casein kinase-1 alpha as one of the phosphotransferases potentially involved in tau hyperphosphorylation. KeywordsInclusion body myositis; Alzheimer's disease; tau protein; protein phosphorylation; protein kinases; casein kinase 1; immunohistochemistry Sporadic inclusion body myositis (s-IBM) is a progressive muscle disease that leads to atrophy of specific muscle groups [12]. Characteristic histopathological findings include vacuolar degeneration of muscle fibers and mononuclear cell inflammation [3]. s-IBM muscle also shares pathobiochemical features with affected neurons in Alzheimer's disease (AD), including the accumulation of β-amyloid peptide [4,32] and the formation of intracellular filamentous inclusions composed of the microtubule associated protein tau [5]. In both s-IBM and AD, the tau proteins incorporated into filaments contain elevated stoichiometries of phosphorylation [23,24] and ubiquitination [6,20]. Depending on the sites occupied, tau hyperphosphorylation

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Casein Kinase 1 Delta Phosphorylates Tau and Disrupts Its Binding to Microtubules

Cited by 136 publications

References 75 publications

Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility

Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility

Tau-induced neurodegeneration: mechanisms and targets

Casein kinase 1 alpha associates with the tau-bearing lesions of inclusion body myositis

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