Journal
FEBS JOURNAL
Volume 281, Issue 23, Pages 5237-5250Publisher
WILEY-BLACKWELL
DOI: 10.1111/febs.13063
Keywords
c-Jun N-terminal kinase (JNK); c-Jun N-terminal kinase-interacting protein 4 (JIP4); itogen-activated protein kinase kinase 4 (MKK4); p38; Sec8
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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.
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