MAP kinase kinase kinases and innate immunity

Toll-like receptors, which respond to invariant microbial molecules, and receptors for the proinflammatory cytokines tumour necrosis factor and interleukin-1 are crucial for initiation and regulation of innate immune responses. These receptors activate each of the major mitogen-activated protein (MAP) kinase subtypes, extracellular signal-regulated protein kinases, c-Jun amino-terminal kinases and p38 MAP kinases, which are crucial for cell survival and controlling the expression of immune mediators. Here we discuss recent studies characterizing the specific MAP kinase kinase kinases (MAP 3-kinases) that link MAP kinases to receptors involved in innate immunity and the mechanisms by which the activity of MAP 3-kinases is regulated by such receptors.