Abstract
MAP kinase-activated protein kinases (MKs), protein serine/threonine kinases downstream of the MAPKs, regulate a number of biological functions. MK5 was initially identified as a substrate for p38 MAPK but subsequent studies revealed that MK5 activity is regulated by atypical MAPKs ERK3 and ERK4. However, the roles of these MAPKs in activating MK5 remain controversial. The interactome and physiological function of MK5 are just beginning to be understood. Here, we provide an overview of the structure-function of MK5 including recent progress in determining its role in cardiac structure and function. The cardiac phenotype of MK5 haplodeficient mice, and the effect of reduced MK5 expression on cardiac remodeling, is also discussed. © 2017 IUBMB Life, 69(10):785-794, 2017.
Keywords:
ERK3; ERK4; MK5; fibroblast; heart; p38 MAPK.
© 2017 International Union of Biochemistry and Molecular Biology.
MeSH terms
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Animals
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Fibroblasts / cytology
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Fibroblasts / enzymology*
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Gene Expression Regulation
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Heart Ventricles / cytology
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Heart Ventricles / enzymology*
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Humans
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Intracellular Signaling Peptides and Proteins / genetics*
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Intracellular Signaling Peptides and Proteins / metabolism
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Mice
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Mitogen-Activated Protein Kinase 6 / genetics*
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Mitogen-Activated Protein Kinase 6 / metabolism
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Myocardium / cytology
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Myocardium / enzymology*
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Myocytes, Cardiac / enzymology
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Myocytes, Cardiac / metabolism
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Protein Domains
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction
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Ventricular Remodeling / genetics
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p38 Mitogen-Activated Protein Kinases / genetics*
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Intracellular Signaling Peptides and Proteins
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Isoenzymes
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MAP-kinase-activated kinase 5
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Protein Serine-Threonine Kinases
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Mitogen-Activated Protein Kinase 6
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p38 Mitogen-Activated Protein Kinases