Subcellular Localization of MAPKs

Because there are several nuclear substrates for the members of the mitogen-activated protein kinase (MAPK) superfamily, they should become localized to the nucleus to achieve their functions. For example, whereas extracellular signal-regulated kinase (ERK) predominantly localizes to the cytoplasm in quiescent cells, it translocates to the nucleus upon its activation by mitogenic stimuli (1 –3 ). Nuclear localization of ERK is transient, however, and ERK is exported from the nucleus to the cytoplasm when it is inactivated. Similarly, ultraviolet irradiation and osmotic stimuli induce activation and transient nuclear localization of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38 MAPKs (4 –6 ). To adequately perform their functions, not only the activation state but also the subcellular localization must be tightly regulated.