Structural highlights
3vut is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Gene: | MAP2K4, JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1 (HUMAN) |
| Activity: | Mitogen-activated protein kinase kinase, with EC number 2.7.12.2 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[MP2K4_HUMAN] 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.[1]
Publication Abstract from PubMed
Mitogen-activated protein kinase kinase 4 (MAP2K4) plays a crucial role in the stress-activated signal cascade and is enzymatically regulated by ligand or substrate binding, and/or post-translational modification. Crystal structures combined with small-angle X-ray scattering experiments revealed that the apo form of non-phosphorylated MAP2K4 (npMAP2K4) exists in a transient state which has a longer conformation compared with the typical kinase folding. Upon ATP-binding, the transient conformation adopted the configuration of typical kinase folding. In the absence of ATP-binding, the transient state of apo npMAP2K4 may shift to a state of aggregation via non-particular hydrophobic interactions as a result of the exposed hydrophobic residues.
Crystal and solution structures disclose a putative transient state of mitogen-activated protein kinase kinase 4.,Matsumoto T, Kinoshita T, Kirii Y, Tada T, Yamano A Biochem Biophys Res Commun. 2012 Aug 24;425(2):195-200. Epub 2012 Jul 22. PMID:22828509[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science. 1995 Apr 14;268(5208):286-90. PMID:7716521
- ↑ Matsumoto T, Kinoshita T, Kirii Y, Tada T, Yamano A. Crystal and solution structures disclose a putative transient state of mitogen-activated protein kinase kinase 4. Biochem Biophys Res Commun. 2012 Aug 24;425(2):195-200. Epub 2012 Jul 22. PMID:22828509 doi:http://dx.doi.org/10.1016/j.bbrc.2012.07.066
