MAP2K4 Protein, Human (sf9, His, StrepⅡ, GST)

MAP2K4, a dual specificity protein kinase, serves as a pivotal component in the MAP kinase signal transduction pathway, particularly in the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling cascade. Teaming up with MAP2K7/MKK7, MAP2K4 stands out as one of the few known kinases capable of directly activating stress-activated protein kinases, including MAPK8/JNK1, MAPK9/JNK2, and MAPK10/JNK3, through phosphorylation of the Thr-Pro-Tyr motif. While both MAP2K4/MKK4 and MAP2K7/MKK7 contribute to JNK activation, their preferences for phosphorylation sites within this motif differ. MAP2K4 favors phosphorylation of the Tyr residue, whereas MAP2K7/MKK7 prefers the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 appears crucial for JNK activation, especially in response to pro-inflammatory cytokines, while other stimuli engage both MAP2K4/MKK4 and MAP2K7/MKK7 in a synergistic phosphorylation of JNKs. Notably, MAP2K4 plays an essential role in maintaining peripheral lymphoid homeostasis and participates in the mitochondrial death signaling pathway, leading to apoptosis. While MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 goes a step further by additionally activating the p38 MAPKs MAPK11, MAPK12, MAPK13, and MAPK14.