Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1494 (By similarity). Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with CDC42 (PubMed:9079650). Interacts with TRAF4; this promotes homodimerization (PubMed:16157600). Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1 (PubMed:15262978). Interacts with GADD45 and MAP2K6 (By similarity). Interacts with ZFP36; this interaction enhances the association with SH3KBP1/CIN85. Interacts with SH3KBP1; this interaction enhances the association with ZFP36 (By similarity). Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles. Widely expressed. High expression was found in skeletal muscle, kidney, testis followed by heart brain and lung. Low expression was found in spleen. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.