ArticleMolecular and cellular biology2005
A novel mitogen-activated protein kinase docking site in the N terminus of MEK5alpha organizes the components of the extracellular signal-regulated kinase 5 signaling pathway.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Structural basis for MEKK2 dimerization and substrate recognition.Nature communications · 2025Article
- Fine Mapping of theFrontiers in genetics · 2022Article
- Targeting MEK5 impairs nonhomologous end-joining repair and sensitizes prostate cancer to DNA damaging agents.Oncogene · 2020Article
- Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition in Cancer.International journal of molecular sciences · 2019Review
- Oncogenic signaling of MEK5-ERK5.Cancer letters · 2017Review
- MEK5 overexpression is associated with the occurrence and development of colorectal cancer.BMC cancer · 2016Article
- The Potential of Vitamin D-Regulated Intracellular Signaling Pathways as Targets for Myeloid Leukemia Therapy.Journal of clinical medicine · 2015Review
- Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1.The EMBO journal · 2014Article
- Review
- Mitogen/extracellular signal-regulated kinase kinase-5 promoter region polymorphisms affect the risk of sporadic colorectal cancer in a southern Chinese population.DNA and cell biology · 2012Article
- MEK5/ERK5 pathway: the first fifteen years.Biochimica et biophysica acta · 2012Review
- Targeted deletion of the extracellular signal-regulated protein kinase 5 attenuates hypertrophic response and promotes pressure overload-induced apoptosis in the heart.Circulation research · 2010Article
- Defining the regulation of KLF4 expression and its downstream transcriptional targets in vascular endothelial cells.Biochemical and biophysical research communications · 2010Article
- MEK5 and ERK5 are mediators of the pro-myogenic actions of IGF-2.Journal of cell science · 2009Article
- A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Selectivity of docking sites in MAPK kinases.The Journal of biological chemistry · 2009Article
- Regulation of neuronal survival by the extracellular signal-regulated protein kinase 5.Cell death and differentiation · 2009Article
- Erk5 controls Slug expression and keratinocyte activation during wound healing.Molecular biology of the cell · 2008Article
- MAP kinase pathways: the first twenty years.Biochimica et biophysica acta · 2007Review
- Noncanonical function of MEKK2 and MEK5 PB1 domains for coordinated extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase signaling.Molecular and cellular biology · 2007Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The alternative splicing of the mek5 gene gives rise to two isoforms. MEK5beta lacks an extended N terminus present in MEK5alpha. Comparison of their activities led us to identify a novel mitogen-activated protein kinase (MAPK) docking site in the N terminus of MEK5alpha that is distinct from the consensus motif identified in the other MAPK kinases. It consists of a cluster of acidic residues at position 61 and positions 63 to 66. The formation of the MEK5/extracellular signal-regulated kinase 5 (ERK5) complex is critical for MEK5 to activate ERK5, to increase transcription via MEF2, and to enhance cellular survival in response to osmotic stress. Certain mutations in the ERK5 docking site that prevent MEK5/ERK5 interaction also abrogate the ability of MEKK2 to bind and activate MEK5. However, the identification of MEK5alpha mutants with selective binding defect demonstrates that the MEK5/ERK5 interaction does not rely on the binding of MEK5alpha to MEKK2 via their respective PB1 domains. Altogether these results establish that the N terminus of MEK5alpha is critical for the specific organization of the components of the ERK5 signaling pathway.
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Registered trials
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.