Abstract
Stress-activated protein kinase-3 (SAPK3) is unique amongst the mitogen-activated protein kinase (MAPK) family with its C-terminal 5 amino acids directing interaction with the PDZ domain-containing substrates alpha1-Syntrophin and SAP90/PSD95. Here, we identify three additional PDZ domain-containing binding partners, Lin-7C, Scribble, and outer membrane protein 25 (OMP25). This latter protein is localised together with SAPK3 at the mitochondria but it is not a SAPK3 substrate. Instead, OMP25 inhibits SAPK3 activity towards PDZ domain-containing substrates such as alpha1-Syntrophin and substrates without PDZ domains such as the mitochondrial protein Sab. This is a new mechanism for the regulation of SAPK3 and suggests that its intracellular activity should not be solely assessed by its phosphorylation status.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / analysis
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Calcium-Binding Proteins / metabolism
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Cells, Cultured
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Humans
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Immunoprecipitation
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Membrane Proteins / analysis
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Membrane Proteins / metabolism*
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Mice
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Mitochondria / chemistry
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Mitochondria / physiology*
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Mitochondrial Proteins / metabolism*
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Mitogen-Activated Protein Kinase 12 / analysis
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Mitogen-Activated Protein Kinase 12 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 12 / metabolism
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Muscle Proteins / metabolism
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Rats
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Substrate Specificity
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Two-Hybrid System Techniques
Substances
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Adaptor Proteins, Signal Transducing
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Calcium-Binding Proteins
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Membrane Proteins
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Mitochondrial Proteins
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Muscle Proteins
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Synj2bp protein, mouse
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syntrophin alpha1
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Mitogen-Activated Protein Kinase 12