Premium
Knockdown of Sec8 enhances the binding affinity of c‐Jun N‐terminal kinase ( JNK )‐interacting protein 4 for mitogen‐activated protein kinase kinase 4 ( MKK 4) and suppresses the phosphorylation of MKK 4, p38, and JNK , thereby inhibiting apoptosis
Author(s) -
Tanaka Toshiaki,
Iino Mitsuyoshi,
Goto Kaoru
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13063
Subject(s) - microbiology and biotechnology , protein kinase a , mitogen activated protein kinase kinase , ask1 , mapk/erk pathway , map kinase kinase kinase , map2k7 , scaffold protein , cyclin dependent kinase 9 , kinase , protein kinase r , cyclin dependent kinase 2 , c raf , chemistry , biology , signal transduction
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 ( JIP 4) 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 JIP 4‐mediated MAPK signaling under apoptotic conditions. It was found that Sec8 binds to and regulates JIP 4, and that knockdown of Sec8 enhances the binding of JIP 4 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. Structured digital abstractSec8 physically interacts with JIP4 by anti tag coimmunoprecipitation ( View interaction ) JIP4 physically interacts with Sec8 by anti bait coip ( View interaction ) Sec8 and JIP4 colocalize by fluorescence microscopy ( View interaction )