p38α stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis

Ackerley, Steven; Grierson, Andrew J.; Banner, Steven J.; Perkinton, Michael S.; Brownlees, Janet; Byers, Helen L.; Ward, Malcolm; Thornhill, Paul; Hussain, Kader; Waby, Jennifer S.; Anderton, Brian H.; Cooper, Jonathan D.; Dingwall, Colin; Leigh, P. Nigel; Miller, Christopher C.J.

doi:10.1016/j.mcn.2004.02.009

Cited by 102 publications

(77 citation statements)

References 67 publications

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“…P38/MAPK could also be up-regulated by a proteasome inhibitor (Yu et al 2004) and it can phosphorylate neurofilaments, too (Ackerley et al 2004). In ALS pathology, JNKJSAPK and p38IMAPK were activated in glial cells and in motor neurons (Migheli et al 1997).…”

Section: Discussionmentioning

confidence: 99%

Proteasome inhibition induces selective motor neuron death in organotypic slice cultures

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Proteasome inhibition induces selective motor neuron death in organotypic slice cultures

et al. 2005

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“…KSPxK motifs are phosphorylated by prolinedirected cyclin-dependent kinase 5 (Cdk5) (Shetty et al, 1993;Sun et al, 1996;Veeranna et al, 1995). Both KSPxK and KSPxxxK sites are phosphorylated by mitogen-activated protein kinases (MAPKs), such as extracellular-signalregulated kinases (Erks) , c-Jun N-terminal kinases (JNKs) (Giasson and Mushynski, 1997) and p38 (MAPK14) (Ackerley et al, 2004), which constitute signaling cascades that respond to growth factors (Li et al, 1999b;Pearson et al, 2001), Ca 2+ influx (Li et al, 1999a), integrins (Li et al, 2001) and myelination (Nixon et al, 1994). Myelination has an effect on NF phosphorylation.…”

Section: Neurofilament Phosphorylationmentioning

confidence: 99%

Neurofilaments at a glance

Yuan

Rao

Veeranna

et al. 2012

Journal of Cell Science

314

233

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“…In an attempt to test this hypothesis, we performed a large scale co-immunoprecipitation to identify proteins that interact with OGT during glucose deprivation (data not shown). One potential target identified by this screen was NF-H, a known substrate of both OGT and p38 (50,51).…”

Section: Ogt Specific Catalytic Activity and [Udp-glcnac] Are Not Incmentioning

confidence: 99%

AMP-activated Protein Kinase and p38 MAPK Activate O-GlcNAcylation of Neuronal Proteins during Glucose Deprivation

Cheung

Hart

2008

Journal of Biological Chemistry

203

258

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We have demonstrated previously that a wide array of stress signals induces O-GlcNAc transferase (OGT) expression and increases O-GlcNAcylation of many intracellular proteins, a response that is critical for cell survival. Here, we describe a mechanism by which glucose deprivation induces OGT expression and activity in Neuro-2a neuroblastoma cells. Glucose deprivation increases OGT mRNA and protein expression in an AMP-activated protein kinase-dependent manner, whereas OGT enzymatic activity is regulated in a p38 MAPK-dependent manner. OGT is not phosphorylated by p38, but rather it interacts directly with p38 through its C terminus; this interaction increases with p38 activation during glucose deprivation. Surprisingly, the catalytic activity of OGT, as measured toward peptide substrates, is not altered by glucose deprivation. Instead, p38 regulates OGT activity within the cell by recruiting it to specific targets, including neurofilament H. Neurofilament H is O-GlcNAcylated during glucose deprivation in a p38-dependent manner. Interestingly, neurofilament H solubility is increased by glucose deprivation in an O-GlcNAc-dependent manner, suggesting that O-GlcNAcylation of neurofilament H regulates its disassembly from filaments. Not only do these data help to reveal how OGT is regulated by stress, but these findings also describe a possible mechanism by which defective brain glucose metabolism, as found in aging and ischemia, may directly affect axonal structure.

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p38α stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis

Cited by 102 publications

References 67 publications

Proteasome inhibition induces selective motor neuron death in organotypic slice cultures

Proteasome inhibition induces selective motor neuron death in organotypic slice cultures

Neurofilaments at a glance

AMP-activated Protein Kinase and p38 MAPK Activate O-GlcNAcylation of Neuronal Proteins during Glucose Deprivation

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