Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Activated by phosphorylation on Thr-530. Binds both upstream activators and downstream substrates in multimolecular complexes. Part of a complex with MAP2K3, RAC1 and CCM2. Interacts with MAP2K5 and SPAG9. Phosphorylation at Ser-166 and Ser-337 by SGK1 inhibits its activity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.