Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation (By similarity). Homodimer; undergoes dimerization during activation. Interacts with MAP2K4/MKK4 (By similarity). Interacts with MAP2K7/MKK7 (PubMed:14575811). Found in a complex with SH3RF1, RAC1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1 (By similarity). Location is cell cycle dependent. Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-278 is likely to be the main autophosphorylation site. Phosphorylation of Ser-556 and Ser-557 is induced by CDC42 (By similarity). Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.