Outer membrane protein 25-a mitochondrial anchor and inhibitor of stress-activated protein kinase-3.
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.
Court
Naomi W
NW
Cell Signalling Laboratory, Biochemistry and Molecular Biology (M310), University of Western Australia, Western Australia 6009, Australia.
Ingley
Evan
E
Klinken
S Peter
SP
Bogoyevitch
Marie A
MA
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D048291:Mitogen-Activated Protein Kinase 12 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; C457224:Synj2bp protein, mouse; C091825:syntrophin alpha1; D048291:Mitogen-Activated Protein Kinase 12