ArticleMolecular and cellular biology2002
Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 153 citations in OpenAlex.
- Gadd45B Deficiency Drives Radio-Resistance in BRAFCancers · 2025Article
- GADD45G operates as a pathological sensor orchestrating reactive gliosis and neurodegeneration.Neuron · 2025Article
- Identification of DNA damage repair-related genes in sepsis using bioinformatics and machine learning: An observational study.Medicine · 2025Observational
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- GADD45β-MTK1 signaling axis mediates oncogenic stress-induced activation of the p38 and JNK pathways.Cancer science · 2025Article
- MAP3K4 kinase action and dual role in cancer.Discover oncology · 2024Review
- A systems and computational biology perspective on advancing CAR therapy.Seminars in cancer biology · 2023Review
- JNK Cascade-Induced Apoptosis-A Unique Role in GqPCR Signaling.International journal of molecular sciences · 2023Review
- Identification of potential diagnostic and prognostic biomarkers for sepsis based on machine learning.Computational and structural biotechnology journal · 2023Article
- Review
- The GADD45G/p38 MAPK/CDC25B signaling pathway enhances neurite outgrowth by promoting microtubule polymerization.iScience · 2022Article
- Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy.The Journal of nutrition · 2022Review
- Gadd45 Proteins in Immunity 2.0.Advances in experimental medicine and biology · 2022Article
- JNK3 as Therapeutic Target and Biomarker in Neurodegenerative and Neurodevelopmental Brain Diseases.Cells · 2020Review
- Sulforaphene inhibits esophageal cancer progression via suppressing SCD and CDH3 expression, and activating the GADD45B-MAP2K3-p38-p53 feedback loop.Cell death & disease · 2020Article
- Transcriptome network of the papillary thyroid carcinoma radiation marker CLIP2.Radiation oncology (London, England) · 2020Article
- Stress-responsive MTK1 SAPKKK serves as a redox sensor that mediates delayed and sustained activation of SAPKs by oxidative stress.Science advances · 2020Article
- HER2/HER3 regulates lactate secretion and expression of lactate receptor mRNA through the MAP3K4 associated protein GIT1.Scientific reports · 2019Article
- Functional Network Analysis Reveals the Relevance of SKIIP in the Regulation of Alternative Splicing by p38 SAPK.Cell reports · 2019Article
- DNA damage response induced by Etoposide promotes steroidogenesis via GADD45A in cultured adrenal cells.Scientific reports · 2018Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
A variety of cellular stresses activate the stress-responsive mitogen-activated protein (MAP) kinases p38 and JNK. In this study, we studied the activation mechanism of a human MAP kinase kinase kinase, MTK1 (also known as MEKK4), which mediates activation of both p38 and JNK. MTK1 has an extensive N-terminal noncatalytic domain composed of approximately 1,300 amino acids. Full-length or near full-length MTK1 is catalytically inactive when expressed in Saccharomyces cerevisiae cells, as it is in mammalian cells. Deletion of a segment including positions 253 to 553 activates kinase, indicating that this segment contains the autoinhibitory domain. In the autoinhibited conformation, the MTK1 kinase domain cannot interact with its substrate, MKK6. By a functional complementation screening with yeast cells, GADD45 proteins (GADD45alpha, beta, and gamma) were identified as MTK1 activators. GADD45 proteins bind a site in MTK1 near the inhibitory domain and relieve autoinhibition. Mutants of full-length MTK1 were isolated that can interact with MKK6 in the absence of the activator GADD45 proteins. These MTK1 mutants are constitutively active, in both yeast and mammalian cells. A model of MTK1 autoinhibition by the N-terminal inhibitory domain and activation by GADD45 binding is presented.
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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.