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Physical association between ABIN‐2 and MEKK2 results selectively blockage of MEKK2 mediated NF‐kappaB and ERK2 but not p38 or JNK’s activation
Author(s) -
Liu WeiKuang,
Chou ChenKung
Publication year - 2006
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.20.4.a38-a
Subject(s) - p38 mitogen activated protein kinases , map kinase kinase kinase , kinase , microbiology and biotechnology , mapk/erk pathway , chemistry , biochemistry , biology
NF‐kappaB can be activated by wide variety of stimuli associated with stress or injury in cells. MEKK/ERK kinase kinase (MEKK) 2/3 belong to the family of serine/threonine kinase, and are regulated by growth factor, cellular stress, and inflammatory cytokines leading to activate ERK, JNK, p38 and NF‐kappaB. Here, we presented evidence to show ABIN‐2 physically interacted with MEKK2 and MEKK3 through the fourth coil‐coil domain of ABIN‐2 and N‐terminal of MEKK2 and 3. Such interaction abolished MEKK2 mediated IKKbeta, and ERK2, and MEKK3 mediated ERK2 phosphorylation. The inhibitory activity of ABIN‐2 to downstream targets of MEKK2 and MEKK3 are very selective, since ERK2 and NF‐kappaB activation, but not the activation of JNK or p38 by MEKK2; ERK2 activation, but not the activation of NF‐kappaB, JNK or p38 by MEKK3 are blocked. Moreover, we demonstrated ABIN‐2 could regulate MEKK2‐mediated cell cycle progression, and this effect was dependent on NF‐kappaB modulation. These observations suggest that ABIN‐2 may participate in multiple signaling pathways to regulate NF‐kappaB and ERK2 activation at a selective manner.