Abstract
One critical component in determining the specificity, and efficiency of MAPK (mitogen-activated protein kinase) substrate phophorylation is the presence of distinct docking domains in the substrate proteins. Docking domains have been shown to be important for the activities of members of the ERK (extracellular-signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 subfamilies of MAPKs towards their substrates. Here, we demonstrate that docking domains also play an important role in ERK5-mediated substrate phosphorylation. The presence of a docking domain promotes both phosphorylation of myocyte enhancer factor, MEF2A, in vitro and its activation in vivo by ERK5. Mutational analysis of the MEF2A docking domain demonstrates that the specificity determinants for ERK5 are similar to those observed with members of the p38 subfamily. A docking domain recognized by ERK5 can direct ERK5 to activate heterologous substrates. Deletion analysis demonstrates that as with other MAPKs, it is the catalytic domain of ERK5 that recognizes the docking domain. Our data therefore extend previous observations on other MAPKs and demonstrate that the requirement for specific docking domains in promoting MAPK action towards substrates is a general property of MAPKs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs / physiology
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Animals
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COS Cells / enzymology
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Catalytic Domain / physiology
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Chlorocebus aethiops
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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DNA-Binding Proteins / physiology
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Enzyme Activation / physiology
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Gene Expression Regulation, Enzymologic / physiology
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Humans
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Kidney / cytology
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Kidney / embryology
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Kidney / enzymology
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MADS Domain Proteins
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MEF2 Transcription Factors
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Mitogen-Activated Protein Kinase 7 / metabolism*
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Mitogen-Activated Protein Kinase 7 / physiology
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Mitogen-Activated Protein Kinases / chemistry*
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / physiology
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Muscle Cells / enzymology
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Muscle Cells / metabolism*
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Myogenic Regulatory Factors
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Peptides / physiology
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Phosphorylation
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Protein Sorting Signals / physiology
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Protein Structure, Tertiary / physiology
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Substrate Specificity / physiology
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Transcription Factors / chemistry
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Transcription Factors / metabolism*
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Transcription Factors / physiology
Substances
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DNA-Binding Proteins
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MADS Domain Proteins
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MEF2 Transcription Factors
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MEF2A protein, human
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Myogenic Regulatory Factors
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Peptides
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Protein Sorting Signals
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Transcription Factors
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Mitogen-Activated Protein Kinase 7
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Mitogen-Activated Protein Kinases