MAP2K7

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically activates MAPK8/JNK1 and MAPK9/JNK2, and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2,MAP3K3/MEKK5, and MAP4K2/GCK. This kinase is involved in the signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found, but only one transcript variant has been supported and defined. [provided by RefSeq]

Full Name

mitogen-activated protein kinase kinase 7

Function

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by pro-inflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074).

Biological Process

Apoptotic processIEA:UniProtKB-KW
Cellular response to sorbitolIEA:Ensembl
Cellular senescenceTAS:Reactome
Fc-epsilon receptor signaling pathwayTAS:Reactome
JNK cascadeISS:BHF-UCL
MAPK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of JNK cascadeIEA:Ensembl
Positive regulation of JUN kinase activityISS:BHF-UCL
Positive regulation of neuron apoptotic processIEA:Ensembl
Positive regulation of telomerase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of telomere cappingManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of telomere maintenance via telomeraseManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIMP:UniProtKB
Response to heatManual Assertion Based On ExperimentIDA:UniProtKB
Response to osmotic stressManual Assertion Based On ExperimentIDA:UniProtKB
Response to tumor necrosis factorManual Assertion Based On ExperimentIDA:UniProtKB
Response to UVManual Assertion Based On ExperimentIDA:UniProtKB
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Stress-activated MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cytoplasm
Nucleus

PTM

Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks).