| Post Translational Modifications | Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks). |
| 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 MAP2K7/MKK7, 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 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. |
| Protein Name | Dual Specificity Mitogen-Activated Protein Kinase Kinase 4Map Kinase Kinase 4Mapkk 4Jnk-Activating Kinase 1Mapk/Erk Kinase 4Mek 4Sapk/Erk Kinase 1Sek1Stress-Activated Protein Kinase Kinase 1Sapk Kinase 1Sapkk-1Sapkk1C-Jun N-Terminal Kinase Kinase 1Jnkk |
| Database Links | Reactome: R-HSA-2559580Reactome: R-HSA-2871796Reactome: R-HSA-450321Reactome: R-HSA-5210891Reactome: R-HSA-5684264 |
| Cellular Localisation | CytoplasmNucleus |
| Alternative Protein Names | Dual Specificity Mitogen-Activated Protein Kinase Kinase 4 proteinMap Kinase Kinase 4 proteinMapkk 4 proteinJnk-Activating Kinase 1 proteinMapk/Erk Kinase 4 proteinMek 4 proteinSapk/Erk Kinase 1 proteinSek1 proteinStress-Activated Protein Kinase Kinase 1 proteinSapk Kinase 1 proteinSapkk-1 proteinSapkk1 proteinC-Jun N-Terminal Kinase Kinase 1 proteinJnkk proteinMAP2K4 proteinJNKK1 proteinMEK4 proteinMKK4 proteinPRKMK4 proteinSEK1 proteinSERK1 proteinSKK1 protein |
Information sourced from Uniprot.org
