Abstract
MEKK3 serves as a critical intermediate signaling molecule in lysophosphatidic acid-mediated nuclear factor-κB (NF-κB) activation. However, the precise regulation for MEKK3 activation at the molecular level is still not fully understood. Here we report the identification of two regulatory phosphorylation sites at Thr-516 and Ser-520 within the kinase activation loop that is essential for MEKK3-mediated IκB kinase β (IKKβ)/NF-κB activation. Substitution of these two residues with alanine abolished the ability of MEKK3 to activate IKKβ/NF-κB, whereas replacement with acidic residues rendered MEKK3 constitutively active. Furthermore, substitution of these two residues with alanine abolished the ability of MEKK3 to mediate lysophosphatidic acid-induced optimal IKKβ/NF-κB activation.
Original language | English (US) |
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Pages (from-to) | 7911-7918 |
Number of pages | 8 |
Journal | Journal of Biological Chemistry |
Volume | 285 |
Issue number | 11 |
DOIs | |
State | Published - Mar 12 2010 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology