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Literature summary extracted from

  • Fritz, A.; Brayer, K.J.; McCormick, N.; Adams, D.G.; Wadzinski, B.E.; Vaillancourt, R.R.
    Phosphorylation of serine 526 is required for MEKK3 activity and association with 14-3-3 blocks dephosphorylation (2006), J. Biol. Chem., 281, 6236-6245.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.11.25 additional information phosphorylation at Ser526 and Thr530 in the activation loop is required for MEKK3 activation, dephosphorylation is blocked by binding to protein 14-3-3 Homo sapiens
2.7.11.25 additional information no change in phosphorylation of Ser526 in the presence or absence of okadaic acid Mus musculus
2.7.11.25 sorbitol induces phosphorylation of Ser526, response to osmotic stress Mus musculus

Application

EC Number Application Comment Organism
2.7.11.25 additional information the association between MEKK3 and 14-3-3 is dependent on Ser526 and prevents dephosphorylation of Ser526 in HEK293 EBNA cells, Ser526 of MEKK3 is an autophosphorylation site within the T-loop that is regulated by PP2A and 14-3-3 proteins synthetic construct

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.11.25 expression of His- or FLAG-tagged wild-type and mutant MEKK3s in HEK293 EBNA cells, co-expression of substrate GST-HA-tagged MKK6 substrate Homo sapiens
2.7.11.25 FLAG-MEKK3 excised from pBTM116 and ligated into the EcoRV site of pcDNA3.1, HEK293 EBNA cells transiently transfected with MEKK3, K391M, or point mutants in the pcDNA3.1 HisA plasmid HisA synthetic construct

Protein Variants

EC Number Protein Variants Comment Organism
2.7.11.25 K391A site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme Homo sapiens
2.7.11.25 K391M catalytically inactive mutant of MEKK3, is not phosphorylated at Ser526, abrogates NF-kappaB luciferase activity synthetic construct
2.7.11.25 S511A can activate the ERK pathway synthetic construct
2.7.11.25 S526A site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme Homo sapiens
2.7.11.25 S526A fails to activate the NF-kappaB luciferase reporter gene and is unable to activate the MEK and ERK pathway synthetic construct
2.7.11.25 S526D site-directed mutagenesis of MEKK3, the mutant shows reduced activity compared to the wild-type enzyme Homo sapiens
2.7.11.25 S526D is capable of activating a NF-kappaB luciferase reporter gene as well as ERK and MEK synthetic construct
2.7.11.25 S526E site-directed mutagenesis of MEKK3, the mutant shows reduced activity compared to the wild-type enzyme Homo sapiens
2.7.11.25 S526E is capable of activating a NF-kappaB luciferase reporter gene as well as ERK and MEK synthetic construct
2.7.11.25 T516A can activate the ERK pathway synthetic construct
2.7.11.25 T520A can activate the ERK pathway synthetic construct
2.7.11.25 T522A can activate the ERK pathway synthetic construct
2.7.11.25 T528A can activate the ERK pathway synthetic construct
2.7.11.25 T530A site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme Homo sapiens
2.7.11.25 T530A fails to activate the NF-kappaB luciferase reporter gene and is unable to activate the MEK and ERK pathway synthetic construct
2.7.11.25 T530D site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme Homo sapiens
2.7.11.25 T530D unable to activate MEKK3-dependent signaling pathways synthetic construct
2.7.11.25 T530E site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme Homo sapiens
2.7.11.25 T530E unable to activate MEKK3-dependent signaling pathways synthetic construct

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.11.25 Mg2+
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.11.25 ATP + MKK6 Homo sapiens
-
 ADP + phosphorylated MKK6
-
 ?
2.7.11.25 additional information Homo sapiens MEKK3 is involved in activation of MAPKs e.g. p38 and JNK ?
-
 ?
2.7.11.25 additional information Mus musculus endogenous MEKK3 is phosphorylated on Ser526 in the response to exogenous stimuli like osmotic stress ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.11.25 Homo sapiens
-
-
-
2.7.11.25 Mus musculus
-
-
-
2.7.11.25 synthetic construct
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.11.25 phosphoprotein phosphorylation at Ser526 and Thr530 in the activation loop is required for MEKK3 activation, dephosphorylation is blocked by binding to protein 14-3-3 Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
2.7.11.25 ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate Lys391 is the catalytic residue Homo sapiens
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.11.25 NIH-3T3 cell
-
 Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.11.25 ATP + ERK MEKK3-dependent activation correlates with a requirement for serine at position 526 synthetic construct ADP + phosphorylated ERK
-
 ?
2.7.11.25 ATP + F-kappaB luciferase Ser526 and Thr530 are required for MEKK3-dependent activity synthetic construct ADP + phosphorylated F-kappaB luciferase
-
 ?
2.7.11.25 ATP + JNK MEKK3-dependent activation correlates with a requirement for serine at position 526 synthetic construct ADP + phosphorylated JNK
-
 ?
2.7.11.25 ATP + MKK6
-
 Homo sapiens ADP + phosphorylated MKK6
-
 ?
2.7.11.25 ATP + MKK6 phosphorylation of Ser526 is required for MKK6 phosphorylation in vitro synthetic construct ADP + phosphorylated MKK6
-
 ?
2.7.11.25 ATP + p38 MEKK3-dependent activation correlates with a requirement for serine at position 526 synthetic construct ADP + phosphorylated p38
-
 ?
2.7.11.25 additional information MEKK3 is involved in activation of MAPKs e.g. p38 and JNK Homo sapiens ?
-
 ?
2.7.11.25 additional information endogenous MEKK3 is phosphorylated on Ser526 in the response to exogenous stimuli like osmotic stress Mus musculus ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.11.25 MAP3K
-
 Mus musculus
2.7.11.25 MAP3K
-
 synthetic construct
2.7.11.25 MAPK/ERKkinase kinase 3
-
 Mus musculus
2.7.11.25 MAPK/ERKkinase kinase 3
-
 synthetic construct
2.7.11.25 MEKK3
-
 Mus musculus
2.7.11.25 MEKK3
-
 Homo sapiens
2.7.11.25 MEKK3
-
 synthetic construct
2.7.11.25 mitogen-activated protein kinase kinase kinase
-
 Mus musculus
2.7.11.25 mitogen-activated protein kinase kinase kinase
-
 synthetic construct

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.11.25 30
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.11.25 7.4 7.5 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.11.25 ATP
-
 Homo sapiens