Activated human JNK kinases (MKK4 and MKK7) phosphorylate Thr183 and Tyr185 residues in the characteristic Thr-Pro-Tyr phosphoacceptor loop of each JNK.
JNK is differentially regulated by MKK4 and MKK7 depending on the stimulus. MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 cascade requires both MKK4 and MKK7. Some studies reported that in three JNK isoforms tested MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine residue (Thr-183).
|p-MAP2K4/p-MAP2K7||JUN kinase kinase activity (0008545)|
|9162092||Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo.||J Biol Chem||1997|
|16186825||Essential function for the kinase TAK1 in innate and adaptive immune responses||Nat Immunol||2005|
|17875933||Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in the nervous system causes severe brain developmental defects and premature death||Mol Cell Biol||2007|