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A novel SAPK/JNK kinase, MKK7, stimulated by TNFα and cellular stresses
Author(s) -
Moriguchi Tetsuo,
Toyoshima Fumiko,
Masuyama Norihisa,
Hanafusa Hiroshi,
Gotoh Yukiko,
Nishida Eisuke
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.23.7045
Subject(s) - biology , microbiology and biotechnology , kinase , tumor necrosis factor alpha , map kinase kinase kinase , protein kinase a , cancer research , endocrinology
Stress‐activated protein kinase (SAPK)/c‐Jun N‐terminal kinase (JNK), a member of the MAP kinase (MAPK) superfamily, is thought to play a key role in a variety of cellular responses. To date, SEK1/MKK4, one of the MAP kinase kinase (MAPKK) family of molecules, is the only SAPK/JNK kinase that has been cloned. Here we have cloned, identified and characterized a novel member of the mammalian MAPKKs, designated MKK7. MKK7 is most similar to the mediator of morphogenesis, hemipterous ( hep ), in Drosophila . Immunochemical studies have identified MKK7 as one of the major SAPK/JNK‐activating kinases in osmotically shocked cells. While SEK1/MKK4 can activate both the SAPK/JNK and p38 subgroups of the MAPK superfamily, MKK7 is specific for the SAPK/JNK subgroup. MKK7 is activated strongly by tumour necrosis factor α (TNFα) as well as by environmental stresses, whereas SEK1/MKK4 is not activated by TNFα. Column fractionation studies have shown that MKK7 is a major activator for SAPK/JNK in the TNFα‐stimulated pathway. Moreover, we have found that overexpression of MKK7 enhances transcription from an AP‐1‐dependent reporter construct. Thus, MKK7 is an evolutionarily conserved MAPKK isoform which is specific for SAPK/JNK, is involved in AP‐1‐dependent transcription and may be a crucial mediator of TNFα signalling.