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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 proinflammatory 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.
Gene Name: | mitogen-activated protein kinase kinase 4 |
Family/Subfamily: | Protein Kinase , MAP2K |
Synonyms: | MAP2K4, JNK activating kinase 1, JNK-activated kinase 1, JNK-activating kinase 1, MAPK/ERK kinase 4, MAPKK4, JNKK1, PRKMK4, SAPKK1, SEK1, MEK4, MKK4, SAPK/ERK kinase 1, SERK1, JNKK, MAP kinase kinase 4, MAPKK 4, MEK 4, SAPK kinase 1, SAPKK-1, SKK1 |
Target Sequences: | NM_003010 NP_003001.1 P45985 |
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