The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors
Open accessAbstract
Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an important event in the conversion of extracellular signals into a cellular response. However, the existence of multiple MAP kinases which phosphorylate similar phosphoacceptor motifs poses a problem in maintaining substrate specificity and hence the correct biological response. Both the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) subfamilies of MAP kinases use a second specificity determinant and require docking to their transcription factor substrates to achieve maximal substrate activation. In this study, we demonstrate that among the different MAP kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2. The efficiency of phosphorylation in vitro and transcriptional activation in vivo of MEF2A and MEF2C by these p38 subtypes requires the presence of a kinase docking domain (D-domain). Furthermore, the D-domain from MEF2A is sufficient to confer p38 responsiveness on different transcription factors, and reciprocal effects are observed upon the introduction of alternative D-domains into MEF2A. These results therefore contribute to our understanding of signalling to MEF2 transcription factors and demonstrate that the requirement for substrate binding by MAP kinases is an important facet of three different subclasses of MAP kinases (ERK, JNK, and p38).
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“It was previously shown that the MAPK binding specificity of full length proteins can be altered by swapping motifs that bind different MAPKs in cell based reporter systems (30).”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [48]
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Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions*
Pearson, G. W., Robinson, F. L., Gibson, T. B., Xu, B.-E., Karandikar, M. S., Berman, K. S., & Cobb, M. H. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.2.0428 · Cited by 4,111
Mechanisms of specificity in protein phosphorylation
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A conserved docking motif in MAP kinases common to substrates, activators and regulators
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Metadata
- Authors
- Yang, S.-H., Galanis, A., & Sharrocks, A. D.
- Affiliations
- Newcastle University (GB)
- Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
- Corresponding author
- Sharrocks, Andrew D.
- ORCID
- Sharrocks, Andrew D.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1999-06-01
- Volume
- 19
- Issue
- 6
- Pages
- 4028-4038
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC104362
- OpenAlex
- W1766090917
- Cited by
- 244
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 3 · 2017: 6 · 2016: 7 · 2015: 7 · 2014: 3 · 2013: 6 · 2012: 7
- FWCI
- 8.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust
- Newcastle University
- Lister Institute of Preventive Medicine
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- p38 MAPK, MEF2 transcription factors, MEF2A, MEF2C, transcriptional activation, MAPK signaling, ERK, JNK, MADS-box transcription factors
- MeSH terms
- Animals, DNA-Binding Proteins, Escherichia coli, HeLa Cells, Humans, Luciferases, Models, Genetic, Phosphorylation, Plasmids, Protein Binding, Protein Kinases, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Time Factors, Transcription Factors, Blotting, Western, Genes, jun, Sequence Homology, Amino Acid, Calcium-Calmodulin-Dependent Protein Kinases, Genes, Reporter, Myogenic Regulatory Factors, COS Cells, Mitogen-Activated Protein Kinases, MADS Domain Proteins, p38 Mitogen-Activated Protein Kinases, ets-Domain Protein Elk-1, MEF2 Transcription Factors
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