MAP2K4
MAP2K4 (mitogen-activated protein kinase kinase 4, also known as MEK4, MKK4, JNKK1 and SEK1) is a dual specificity protein kinase in the MAP kinase signal transduction pathway. It activates the JNK and p38 stress-activated MAP kinases by phosphorylation. Browse Assay Genie's current range of MAP2K4 research reagents below, or read on for the biology behind the target.
MAP2K4 is an essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway. Together with MAP2K7 (MKK7), it is one of the only known kinases to directly activate the JNKs MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. Both kinases phosphorylate the Thr-Pro-Tyr motif of JNK, but MAP2K4 prefers the tyrosine residue while MAP2K7 prefers the threonine residue. Phosphorylation of the threonine by MAP2K7 appears to be a prerequisite for JNK activation in response to pro-inflammatory cytokines, whereas other stimuli activate both kinases, which then phosphorylate JNKs synergistically. Unlike MAP2K7, which activates only JNKs, MAP2K4 also activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.
The MAP2K4 gene encodes a member of the MAPK family, whose members integrate multiple biochemical signals and take part in proliferation, differentiation, transcription regulation and development. These kinases form a three-tiered module of MAPKKKs, MAPKKs and MAPKs. The MAP2K4 protein is phosphorylated on serine and threonine residues by MAPKKKs, and then phosphorylates downstream MAPK targets on threonine and tyrosine residues. It belongs to the STE Ser/Thr protein kinase family, MAP kinase kinase subfamily, and is found in the cytoplasm and nucleus. Alternative splicing produces multiple transcript variants, and a pseudogene lies on the long arm of chromosome X.
MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK pathway is also involved in mitochondrial death signalling, including cytochrome c release, which leads to apoptosis. A similar protein in mouse (Map2k4) has been reported to play a role in liver organogenesis. The protein was formerly named SAPK/ERK kinase 1, which is the origin of the aliases SEK1 and SERK1.
MAP2K4 is an essential component of the SAP/JNK pathway and directly activates JNK1, JNK2 and JNK3 by phosphorylation.
MAP2K4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14, which distinguishes it from MAP2K7.
The MKK/JNK pathway contributes to mitochondrial death signalling, including cytochrome c release, leading to apoptosis.
MAP2K4 is required for peripheral lymphoid homeostasis, and the mouse protein has been linked to liver organogenesis.
MAP2K4 is a dual specificity kinase that activates the JNKs (JNK1, JNK2, JNK3) and the p38 MAPKs by phosphorylation. It prefers the tyrosine residue of the JNK Thr-Pro-Tyr motif and works with MAP2K7, which prefers the threonine residue.
MAP2K4 is also called MEK4, MKK4, MAPKK4, JNKK1, JNKK, SEK1, SERK1, SAPKK1, SKK1 and PRKMK4. Its previous name was SAPK/ERK kinase 1. Alternative splicing gives multiple transcript variants, and its enzyme classification is EC 2.7.12.2.
A mouse ortholog, Map2k4, exists, and a similar mouse protein has been reported to play a role in liver organogenesis. MAP2K7 activates only JNKs, whereas MAP2K4 also activates p38 MAPKs. Check the datasheet of any product for its validated reactivity.
Other MAP kinase kinases and upstream MAPKKKs in the JNK and p38 signalling cascades with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P45985; product specifications from Assay Genie datasheets.