ArticleThe Journal of biological chemistry2009
Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel MAPK interaction motif.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Intracellular pH regulates ubiquitin-mediated degradation of the MAP kinase ERK3.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Atypical MAPKs in cancer.The FEBS journal · 2025Review
- Review
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Consolidating the association of biallelicJournal of medical genetics · 2023Article
- Expanding the novel MAPKAPK5-related developmental disorder's genotype-phenotype correlation: Patient report and 19 months of follow-up.Clinical genetics · 2022Article
- Crystal Structure and Inhibitor Identifications Reveal Targeting Opportunity for the Atypical MAPK Kinase ERK3.International journal of molecular sciences · 2020Article
- Article
- Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury.Cell & bioscience · 2020Article
- Germ Line Deletion Reveals a Nonessential Role of Atypical Mitogen-Activated Protein Kinase 6/Extracellular Signal-Regulated Kinase 3.Molecular and cellular biology · 2019Article
- MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT/mTOR signaling.The Journal of clinical investigation · 2019Article
- MicroRNA-26a targets MAPK6 to inhibit smooth muscle cell proliferation and vein graft neointimal hyperplasia.Scientific reports · 2017Article
- Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2.Scientific reports · 2017Article
- MAPK-Activated Protein Kinases (MKs): Novel Insights and Challenges.Frontiers in cell and developmental biology · 2015Review
- Comparative Analysis of Two Gene-Targeting Approaches Challenges the Tumor-Suppressive Role of the Protein Kinase MK5/PRAK.PloS one · 2015Article
- A novel role for atypical MAPK kinase ERK3 in regulating breast cancer cell morphology and migration.Cell adhesion & migration · 2015Article
- PRAK interacts with DJ-1 and prevents oxidative stress-induced cell death.Oxidative medicine and cellular longevity · 2014Article
- Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module.The Journal of biological chemistry · 2013Article
- Tumour promoting and suppressing roles of the atypical MAP kinase signalling pathway ERK3/4-MK5.Journal of molecular signaling · 2012Article
- The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology.Molecular and cellular biology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ERK3 and ERK4 are atypical MAPKs in which the canonical TXY motif within the activation loop of the classical MAPKs is replaced by SEG. Both ERK3 and ERK4 bind, translocate, and activate the MAPK-activated protein kinase (MK) 5. The classical MAPKs ERK1/2 and p38 interact with downstream MKs (RSK1-3 and MK2-3, respectively) through conserved clusters of acidic amino acids, which constitute the common docking (CD) domain. In contrast to the classical MAPKs, the interaction between ERK3/4 and MK5 is strictly dependent on phosphorylation of the SEG motif of these kinases. Here we report that the conserved CD domain is dispensable for the interaction of ERK3 and ERK4 with MK5. Using peptide overlay assays, we have defined a novel MK5 interaction motif (FRIEDE) within both ERK4 and ERK3 that is essential for binding to the C-terminal region of MK5. This motif is located within the L16 extension lying C-terminal to the CD domain in ERK3 and ERK4 and a single isoleucine to lysine substitution in FRIEDE totally abrogates binding, activation, and translocation of MK5 by both ERK3 and ERK4. These findings are the first to demonstrate binding of a physiological substrate via this region of the L16 loop in a MAPK. Furthermore, the link between activation loop phosphorylation and accessibility of the FRIEDE interaction motif suggests a switch mechanism for these atypical MAPKs in which the phosphorylation status of the activation loop regulates the ability of both ERK3 and ERK4 to bind to a downstream effector.
Indexed as
Identifiers
What OpenQuestion holds
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.