title: Knockdown of Sec8 enhances the binding affinity of c-Jun N-terminal kinase (JNK)-interacting protein 4 for mitogen-activated protein kinase kinase 4 (MKK4) and suppresses the phosphorylation of MKK4, p38, and JNK, thereby inhibiting apoptosis.
abstract: The exocyst complex, also called the Sec6/8 complex, is important for targeting exocytic vesicles to specific docking sites on the plasma membrane in yeast and mammalian cells. In addition to these original findings, recent results of studies suggest that Sec8 is also involved in oncogenesis, although the functional implications of Sec8 in cancer cells are not well understood. c-Jun N-terminal kinase-interacting protein 4 (JIP4) is a scaffold protein that plays a crucial role in the regulation of mitogen-activated protein kinase (MAPK) signaling cascades. The present study examined how Sec8 is involved in JIP4-mediated MAPK signaling under apoptotic conditions. It was found that Sec8 binds to and regulates JIP4, and that knockdown of Sec8 enhances the binding of JIP4 to MAPK kinase 4, thereby decreasing the phosphorylation of MAPK kinase 4, JNK, and p38. These results raise the possibility that Sec8 serves as an important regulator of MAPK signaling cascades.
authors.affiliation: Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Japan; Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, Yamagata University School of Medicine, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Iino
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D033921:Vesicular Transport Proteins / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C489607:EXOC4 protein, human; C111047:SPAG9 protein, human; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; D003609:Dactinomycin; D003513:Cycloheximide; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human
keywords: Sec8; c-Jun N-terminal kinase (JNK); c-Jun N-terminal kinase-interacting protein 4 (JIP4); mitogen-activated protein kinase kinase 4 (MKK4); p38