In mammalian cells, a variety of extracellular stimuli generate intracellular signals that converge on a limited number of so-called mitogen-activated protein (MAP) kinase pathways. The central core of each MAP kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. Mek1/2 MAPK kinases are essential for mammalian development, homeostasis, and Raf-induced hyperplasia. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.