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Phosphorylation of Thr-516 and Ser-520 in the Kinase Activation Loop of MEKK3 Is Required for Lysophosphatidic Acid-mediated Optimal IκB Kinase β (IKKβ)/Nuclear Factor-κB (NF-κB) Activation
- Source :
- Journal of Biological Chemistry. 285:7911-7918
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- MEKK3 serves as a critical intermediate signaling molecule in lysophosphatidic acid-mediated nuclear factor-kappaB (NF-kappaB) 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 IkappaB kinase beta (IKKbeta)/NF-kappaB activation. Substitution of these two residues with alanine abolished the ability of MEKK3 to activate IKKbeta/NF-kappaB, 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 IKKbeta/NF-kappaB activation.
- Subjects :
- Threonine
Molecular Sequence Data
MAP Kinase Kinase Kinase 3
IκB kinase
Biology
Kidney
Biochemistry
Antibodies
chemistry.chemical_compound
Antibody Specificity
Lysophosphatidic acid
Serine
Animals
Humans
Amino Acid Sequence
Phosphorylation
Luciferases
Molecular Biology
Cells, Cultured
Protein Kinase C
Protein kinase C
Alanine
Interleukin-6
Kinase
NF-kappa B
I-Kappa-B Kinase
Cell Biology
I-kappa B Kinase
chemistry
Mutagenesis, Site-Directed
Rabbits
Lysophospholipids
Signal transduction
Cell Division
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 285
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....9a40fc550f84ca5d14982d8883fa7694