Overview:

MEKK4 is one of the MAPKKKs which mediates activation of both p38 and JNK. N-terminal region of MEKK4 contains an autoinhibitory domain that interacts with the C-terminal kinase domain, inhibits kinase activity and prevents interaction with its substrate, MKK6. MEKK4 is activated upon binding of GADD45 by the stress-inducible GADD45 family of proteins (GADD45α/β/γ). GADD45 binds to the N-terminal region of MEKK4 releasing inhibition of the kinase domain by the autoinhibitory domain (1). MEKK4 is strongly expressed in the developing neuroepithelium and is critical for neural tube closure (2).

Gene Aliases:

MAPKKK4; MEKK 4; MEKK4; MTK1; PRO0412

Genbank Number:

NM_005922

References:

1. Mita, H. et al: Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding. Mol Cell Biol. 2002; 22(13):4544-4555. doi:10.1128/mcb.22.13.4544-4555.2002.

2. Chi, H. et al: Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube development. Proc Natl Acad Sci U S A. 2005; 102(10):3846-385.