Extra-cellular signals, e.g. growth factors, and stress, e.g. UVR, respectively, stimulate a protein kinase cascade ultimately activating MAPKs and directing their nuclear translocation. The MAPK family comprises extra-cellular signal activated protein kinase (ERK) and stress activated protein kinases (SAPKs) which are preferentially activated by physiological or stress stimuli, respectively. Nuclear MAPKs phosphorylate and increase the action of transription factors, e.g. c-Jun, resulting in gene expression changes. (B) The NF-κB pathway: The trancription factor NF-κB is sequestered and inactivated by association with the inhibitor of κB (I-κB) in the cytosol. In response to, e.g. cytokines or UVR, the I–κB kinase (IKK) and, in conjunction with p38, casein kinase 2 (CK2), respectively, phosphorylate I–κB at different serine/threonine residues targeting it for degradation. This releases NF–κB to enter the nucleus and to regulate gene expression. MAPKKK: MAPK kinase kinase; MAPKK: MAPK kinase; MAPK: MAP kinase.