ArticleProtein science : a publication of the Protein Society2021
The interaction of p38 with its upstream kinase MKK6.
Article in Protein science : a publication of the Protein Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- Modulation of p38 MAPK signaling in spinal cord injury by curcumin: targeting inflammation, oxidative stress, and apoptosis.Inflammopharmacology · 2026Review
- Adaptor-mediated rewiring of FLT3 signaling engages p38 MAPK to sustain gilteritinib resistance in acute myeloid leukemia.Leukemia · 2026Article
- Lipid Pocket Binders Impose Allosteric Changes of Protein Dynamics Around the Active Site of the Protein Kinase p38α.Angewandte Chemie (International ed. in English) · 2026Article
- The inflammatory path toward type 1 diabetes begins during pregnancy.Nature communications · 2026Article
- Article
- Long-term dynamic profiles of cognitive kinases induced by different learning protocols.bioRxiv : the preprint server for biology · 2025Article
- Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Male Mice.Biological psychiatry global open science · 2025Article
- Linear motif specificity in signaling through p38α and ERK2 mitogen-activated protein kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- SAMHD1, positively regulated by KLF4, suppresses the proliferation of gastric cancer cells through MAPK p38 signaling pathway.Cell cycle (Georgetown, Tex.) · 2022Article
- The interaction of p38 with its upstream kinase MKK6.Protein science : a publication of the Protein Society · 2021Article
- Long-term dynamic profiles of cognitive kinases induced by different learning protocols.Learning & memory (Cold Spring Harbor, N.Y.)Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mitogen-activated protein kinase (MAPK; p38, ERK, and JNK) cascades are evolutionarily conserved signaling pathways that regulate the cellular response to a variety of extracellular stimuli, such as growth factors and interleukins. The MAPK p38 is activated by its specific upstream MAPK kinases, MKK6 and MKK3. However, a comprehensive molecular understanding of how these cognate upstream kinases bind and activate p38 is still missing. Here, we combine NMR spectroscopy and isothermal titration calorimetry to define the binding interface between full-length MKK6 and p38. It was shown that p38 engages MKK6 not only via its hydrophobic docking groove, but also influences helix αF, a secondary structural element that plays a key role in organizing the kinase core. It was also shown that, unlike MAPK phosphatases, the p38 conserved docking (CD) site is much less affected by MKK6 binding. Finally, it was demonstrated that these interactions with p38 are conserved independent of the MKK6 activation state. Together, the results revealed differences between specificity markers of p38 regulation by upstream kinases, which do not effectively engage the CD site, and downstream phosphatases, which require the CD site for productive binding.
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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.