ArticleJournal of neurochemistry2008
Neurofilament tail phosphorylation: identity of the RT-97 phosphoepitope and regulation in neurons by cross-talk among proline-directed kinases.
Article in Journal of neurochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Vasculocentric Axonal NfH in Small Vessel Disease.Journal of neuropathology and experimental neurology · 2022Article
- Influence of a GSK3β phosphorylation site within the proximal C-terminus of Neurofilament-H on neurofilament dynamics.Biology open · 2017Article
- Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases.Neurobiology of disease · 2017Review
- Loss of prion protein leads to age-dependent behavioral abnormalities and changes in cytoskeletal protein expression.Molecular neurobiology · 2014Article
- The high molecular weight neurofilament subunit plays an essential role in axonal outgrowth and stabilization.Biology open · 2014Article
- Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics.Journal of cell science · 2014Article
- Ectopic expression of transcription factor AP-2δ in developing retina: effect on PSA-NCAM and axon routing.Journal of neurochemistry · 2014Article
- Post-translational modifications of intermediate filament proteins: mechanisms and functions.Nature reviews. Molecular cell biology · 2014Review
- PKIS: computational identification of protein kinases for experimentally discovered protein phosphorylation sites.BMC bioinformatics · 2013Article
- Charcot-Marie-Tooth causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments.Acta neuropathologica · 2013Article
- A neuronal death model: overexpression of neuronal intermediate filament protein peripherin in PC12 cells.Journal of biomedical science · 2012Article
- Article
- Declining phosphatases underlie aging-related hyperphosphorylation of neurofilaments.Neurobiology of aging · 2011Article
- Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration.Molecular vision · 2011Article
- Quantitative phosphoproteomic analysis of neuronal intermediate filament proteins (NF-M/H) in Alzheimer's disease by iTRAQ.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue.Molecular pain · 2009Article
- Myosin Va increases the efficiency of neurofilament transport by decreasing the duration of long-term pauses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
As axons myelinate, establish a stable neurofilament network, and expand in caliber, neurofilament proteins are extensively phosphorylated along their C-terminal tails, which is recognized by the monoclonal antibody, RT-97. Here, we demonstrate in vivo that RT-97 immunoreactivity (IR) is generated by phosphorylation at KSPXK or KSPXXXK motifs and requires flanking lysines at specific positions. extracellular signal regulated kinase 1,2 (ERK1,2) and pERK1,2 levels increase in parallel with phosphorylation at the RT-97 epitope during early postnatal brain development. Purified ERK1,2 generated RT-97 on both KSP motifs on recombinant NF-H tail domain proteins, while cdk5 phosphorylated only KSPXK motifs. RT-97 epitope generation in primary hippocampal neurons was regulated by extensive cross-talk among ERK1,2, c-Jun N-terminal kinase 1,2 (JNK1,2) and cdk5. Inhibition of both ERK1,2 and JNK1,2 completely blocked RT-97 generation. Cdk5 influenced RT-97 generation indirectly by modulating JNK activation. In mice, cdk5 gene deletion did not significantly alter RT-97 IR or ERK1,2 and JNK activation. In mice lacking the cdk5 activator P35, the partial suppression of cdk5 activity increased RT-97 IR by activating ERK1,2. Thus, cdk5 influences RT-97 epitope generation partly by modulating ERKs and JNKs, which are the two principal kinases regulating neurofilament phosphorylation. The regulation of a single target by multiple protein kinases underscores the importance of monitoring other relevant kinases when the activity of a particular one is blocked.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.