Gene Summary: This MAP2K4 gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. MKK4 is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK3. MKK4 is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of MKK4 in mediating survival signal in T cell development, as well as in the organogenesis of liver. [provided by RefSeq, Jul 2008]General information above from NCBI
Catalytic activity: ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation: Activated in response to a variety of cellular stresses, including UV and gamma-irradiation, heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK.
Subunit structure: Interacts with SPAG9 (By similarity). Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3.
Domain: The DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.
The D domain (residues 34-52) contains a conserved docking site and is required for the binding to MAPK substrates.
Subcellular location: Cytoplasm (By similarity). Nucleus (By similarity).
Tissue specificity: Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.
Post-translational: Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks).
Sequence similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Contains 1 protein kinase domain.
General information above from UniProt