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Literature summary for 2.7.11.25 extracted from
- Phosphorylation of serine 526 is required for MEKK3 activity and association with 14-3-3 blocks dephosphorylation (2006), J. Biol. Chem., 281, 6236-6245.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 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 | |
| additional information | no change in phosphorylation of Ser526 in the presence or absence of okadaic acid | Mus musculus | |
| sorbitol | induces phosphorylation of Ser526, response to osmotic stress | Mus musculus |  |
Application
| Application | Comment | Organism |
|---|---|---|
| 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)
| Cloned (Comment) | Organism |
|---|---|
| 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 |
| 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
| Protein Variants | Comment | Organism |
|---|---|---|
| K391A | site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme | Homo sapiens |
| K391M | catalytically inactive mutant of MEKK3, is not phosphorylated at Ser526, abrogates NF-kappaB luciferase activity | synthetic construct |
| S511A | can activate the ERK pathway | synthetic construct |
| S526A | site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme | Homo sapiens |
| S526A | fails to activate the NF-kappaB luciferase reporter gene and is unable to activate the MEK and ERK pathway | synthetic construct |
| S526D | site-directed mutagenesis of MEKK3, the mutant shows reduced activity compared to the wild-type enzyme | Homo sapiens |
| S526D | is capable of activating a NF-kappaB luciferase reporter gene as well as ERK and MEK | synthetic construct |
| S526E | site-directed mutagenesis of MEKK3, the mutant shows reduced activity compared to the wild-type enzyme | Homo sapiens |
| S526E | is capable of activating a NF-kappaB luciferase reporter gene as well as ERK and MEK | synthetic construct |
| T516A | can activate the ERK pathway | synthetic construct |
| T520A | can activate the ERK pathway | synthetic construct |
| T522A | can activate the ERK pathway | synthetic construct |
| T528A | can activate the ERK pathway | synthetic construct |
| T530A | site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme | Homo sapiens |
| T530A | fails to activate the NF-kappaB luciferase reporter gene and is unable to activate the MEK and ERK pathway | synthetic construct |
| T530D | site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme | Homo sapiens |
| T530D | unable to activate MEKK3-dependent signaling pathways | synthetic construct |
| T530E | site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme | Homo sapiens |
| T530E | unable to activate MEKK3-dependent signaling pathways | synthetic construct |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | - |
Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + MKK6 | Homo sapiens | - |
ADP + phosphorylated MKK6 | - |
? | |
| additional information | Homo sapiens | MEKK3 is involved in activation of MAPKs e.g. p38 and JNK | ? | - |
? | |
| additional information | Mus musculus | endogenous MEKK3 is phosphorylated on Ser526 in the response to exogenous stimuli like osmotic stress | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
| synthetic construct | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| 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
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate | Lys391 is the catalytic residue | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| NIH-3T3 cell | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + ERK | MEKK3-dependent activation correlates with a requirement for serine at position 526 | synthetic construct | ADP + phosphorylated ERK | - |
? | |
| ATP + F-kappaB luciferase | Ser526 and Thr530 are required for MEKK3-dependent activity | synthetic construct | ADP + phosphorylated F-kappaB luciferase | - |
? | |
| ATP + JNK | MEKK3-dependent activation correlates with a requirement for serine at position 526 | synthetic construct | ADP + phosphorylated JNK | - |
? | |
| ATP + MKK6 | - |
Homo sapiens | ADP + phosphorylated MKK6 | - |
? | |
| ATP + MKK6 | phosphorylation of Ser526 is required for MKK6 phosphorylation in vitro | synthetic construct | ADP + phosphorylated MKK6 | - |
? | |
| ATP + p38 | MEKK3-dependent activation correlates with a requirement for serine at position 526 | synthetic construct | ADP + phosphorylated p38 | - |
? | |
| additional information | MEKK3 is involved in activation of MAPKs e.g. p38 and JNK | Homo sapiens | ? | - |
? | |
| additional information | endogenous MEKK3 is phosphorylated on Ser526 in the response to exogenous stimuli like osmotic stress | Mus musculus | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| MAP3K | - |
Mus musculus |
| MAP3K | - |
synthetic construct |
| MAPK/ERKkinase kinase 3 | - |
Mus musculus |
| MAPK/ERKkinase kinase 3 | - |
synthetic construct |
| MEKK3 | - |
Mus musculus |
| MEKK3 | - |
Homo sapiens |
| MEKK3 | - |
synthetic construct |
| mitogen-activated protein kinase kinase kinase | - |
Mus musculus |
| mitogen-activated protein kinase kinase kinase | - |
synthetic construct |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.4 | 7.5 | assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
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