GO:0008349:   MAP kinase kinase kinase kinase activity
Catalysis of the phosphorylation of serine and threonine residues in a mitogen-activated protein kinase kinase kinase (MAPKKK), resulting in activation of MAPKKK. MAPKKK signaling pathways relay, amplify and integrate signals from the plasma membrane to the nucleus in response to a diverse range of extracellular stimuli.