6ib0

Structural highlights

Function

[MP2K7_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 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 proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.^{[1] [2] [3]} [:]

References

1. ↑ Wu Z, Wu J, Jacinto E, Karin M. Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase. Mol Cell Biol. 1997 Dec;17(12):7407-16. PMID:9372971
2. ↑ Lu X, Nemoto S, Lin A. Identification of c-Jun NH2-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38. J Biol Chem. 1997 Oct 3;272(40):24751-4. PMID:9312068
3. ↑ Foltz IN, Gerl RE, Wieler JS, Luckach M, Salmon RA, Schrader JW. Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli. J Biol Chem. 1998 Apr 10;273(15):9344-51. PMID:9535930
4. ↑ Wolle P, Hardick J, Cronin SJF, Engel J, Baumann M, Lategahn J, Penninger JM, Rauh D. Targeting the MKK7-JNK (Mitogen-Activated Protein Kinase Kinase 7-c-Jun N-Terminal Kinase) Pathway with Covalent Inhibitors. J Med Chem. 2019 Feb 21. doi: 10.1021/acs.jmedchem.9b00102. PMID:30768270 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b00102