Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways. 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-806. Catalytically active only when complexed with MAP3K5, with MAP3K5 supporting the stability and the active configuration of MAP3K6 and MAP3K6 activating MAP3K5 by direct phosphorylation. Binds both upstream activators and downstream substrates in multimolecular complexes. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.