ArticleThe Journal of biological chemistry2011
The extracellular regulated kinase-1 (ERK1) controls regulated alpha-secretase-mediated processing, promoter transactivation, and mRNA levels of the cellular prion protein.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- An antidepressant decreases CSF Aβ production in healthy individuals and in transgenic AD mice.Science translational medicine · 2014Trial
- Article
- A Bioengineering Strategy to Control ADAM10 Activity in Living Cells.International journal of molecular sciences · 2023Article
- Article
- Tau Protein as a New Regulator of Cellular Prion Protein Transcription.Molecular neurobiology · 2020Article
- Transgenic Overexpression of the Disordered Prion Protein N1 Fragment in Mice Does Not Protect Against Neurodegenerative Diseases Due to Impaired ER Translocation.Molecular neurobiology · 2020Article
- The emerging role of ADAM metalloproteinases in immunity.Nature reviews. Immunology · 2018Review
- ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy?Frontiers in cell and developmental biology · 2016Review
- Unified theory of Alzheimer's disease (UTAD): implications for prevention and curative therapy.Journal of molecular psychiatry · 2016Review
- Article
- Alzheimer's and prion diseases: PDK1 at the crossroads.Nature medicine · 2013Article
- Dissociation of ERK signalling inhibition from the anti-amyloidogenic action of synthetic ceramide analogues.Clinical science (London, England : 1979) · 2012Article
- α-Secretase-derived fragment of cellular prion, N1, protects against monomeric and oligomeric amyloid β (Aβ)-associated cell death.The Journal of biological chemistry · 2012Article
- Proteolytic processing of the prion protein in health and disease.American journal of neurodegenerative disease · 2012Article
- Review
- Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The α-secretases A disintegrin and metalloprotease 10 (ADAM10) and ADAM17 trigger constitutive and regulated processing of the cellular prion protein (PrP(c)) yielding N1 fragment. The latter depends on protein kinase C (PKC)-coupled M1/M3 muscarinic receptor activation and subsequent phosphorylation of ADAM17 on its intracytoplasmic threonine 735. Here we show that regulated PrP(c) processing and ADAM17 phosphorylation and activation are controlled by the extracellular-regulated kinase-1/MAP-ERK kinase (ERK1/MEK) cascade. Thus, reductions of ERK1 or MEK activities by dominant-negative analogs, pharmacological inhibition, or genetic ablation all impair N1 secretion, whereas constitutively active proteins increase N1 recovery in the conditioned medium. Interestingly, we also observed an ERK1-mediated enhanced expression of PrP(c). We demonstrate that the ERK1-associated increase in PrP(c) promoter transactivation and mRNA levels involve transcription factor AP-1 as a downstream effector. Altogether, our data identify ERK1 as an important regulator of PrP(c) cellular homeostasis and indicate that this kinase exerts a dual control of PrP(c) levels through transcriptional and post-transcriptional mechanisms.
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