Dual-specificity mitogen-activated protein kinase kinase 4 is anenzyme that in humans is encoded by theMAP2K4gene.[5]
MAP2K4 encodes adual-specificity kinase that belongs to theSer/Thr protein kinase family. MAP2K4 phosphorylatesMAP kinases in response to various environmental stresses or mitogenic stimuli.MAPK8/JNK1,MAPK9/JNK2, andMAPK14/p38 are substrates for MAP2K4, but MAPK1/ERK2 and MAPK3/ERK1 are not phosphorylated by MAP2K4. Structurally, MAP2K4 contains akinase domain that is phosphorylated and activated byMAP3K1(aka MEKK1).[6] MAP2K4 contains multipleamino acid sites that arephosphorylated andubiquitinated.[7] Genetic studies usingMap2k4 knockout mice revealed embryonic lethality, impaired hepatogenesis and defective liver formation.[8][9] Analysis of chimeric mice identified a role forMap2k4 in T cell cytokine production and proliferation.[10]Map2k4-deficient chimeric mice frequently developlymphadenopathy.[11] MAP2K4 is altered in 1.97% of all human cancers.[12]
MAP2K4 has been shown tointeract with: