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Oxidative inhibition of MAPKAP kinase 2 is predominately mediated through the activation loop cysteine
Author(s) -
Rye Emily Anne,
Forsberg Brian,
Johansen Allan,
Patel Rutvi,
Schumacher Carol,
Chrestensen Carol Ann
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.565.7
Subject(s) - ask1 , map kinase kinase kinase , kinase , protein kinase a , mitogen activated protein kinase kinase , map2k7 , cysteine , chemistry , biochemistry , cyclin dependent kinase 9 , protein kinase c , microbiology and biotechnology , p38 mitogen activated protein kinases , oxidative stress , cyclin dependent kinase 2 , biology , enzyme
MAPKAP kinase 2 (MK2) is a member of the m itogen a ctivated p rotein k inase a ctivated p rotein kinase family. MK2 is activated by p38 MAP kinase and this signaling pathway is important in cellular responses to inflammatory cytokines and stress ( e.g. UV, osmotic shock, oxidative stress). Mammalian MK2 has 7 conserved cysteines, that are not known to participate in disulfide bonds. Among these is a cysteine residue in the activation loop that is conserved in other kinases including protein kinase A (PKA) and protein kinase C (PKC). PKA and PKC are inhibited by oxidative modification at this conserved cysteine residue. Two non‐radioactive assays were used to assess MK2 activity after various treatments using either bacterially expressed active‐MK2 or myc tagged MK2 immunoprecipitated from transiently transfected cells. MK2 was inhibited by oxidized glutathione in vitro and in cells by treatment with diamide. Mutation of the activation loop cysteine residue produced an active kinase that was considerably less sensitive to oxidative inhibition. This work was supported by the Research Corporation (CC6942), the NSF (MCB‐1020261), and a Mentor Protégé grant from Kennesaw State University.