The Ras signaling pathway links signals from growth factor receptors to activation of the MEK/ERK kinases. This cascade of phosphorylation leads to cell growth and differentiation. External stimuli such as endotoxins, UV irradiation, heat, and hyperosmolarity, induce an array of cellular responses that culminate with gene expression. These processes are controlled by the MKK3/p38MAP kinase cascade. A third pathway responsive to environmental stress, cell death, or apoptosis is regulated by SEK/SAPKs. When overexpresssed, MEKK3 is a kinase that is capable of activating both the ERK and SAPK cascades. MEKK3 is 626 amino acids long and is ubiquitously expressed. It is positioned upstream of SEK and MEK in the signaling pathways and directly phosphorylates these enzymes. Overexpression of MEKK3 results in the activation of NFκB. Thus, MEKK3 represents an emerging family of kinases that is capable of inducing more than one signaling pathway. This indicates that specificity in the signaling cascades is probably achieved by effector kinases such as the ERKs and SAPKs.