MAPKAPK2, a target of
p38 MAPK, is shown to be exported from the nucleus to the cytoplasm upon its activation in mammalian cells. This nuclear export is believed to be dependent on its nuclear export signal (NES). Here, we have examined intracellular dynamics of C. elegans MAPKAPK2 (C44C8.6) during whole processes of development. To visualize subcellular localization of MAPKAPK2 in living C. elegans, we constructed a fusion between GFP and MAPKAPK2 under the control of its own promoter. This construct was expressed in late embryo, all larval stages and adults. In adults, MAPKAPK2-GFP was expressed mainly in neuron, neuroblast and vulva. MAPKAPK2-GFP was present mainly in the nucleus of those cells. However, in response to extracellular stresses that induce activation of P38 MAPK and MAPKAPK2, MAPKAPK2-GFP was completely exported from the nucleus to the cytoplasm. An NES-disrupted form of MAPKAPK2 was not exported from the nucleus under any conditions. In addition, RNAi with C. elegans CRM1, which is known as an NES receptor, resulted in the inhibition of nuclear export of MAPKAPK2. These results define the requirement of the NES of MAPKAPK2 for its nuclear export. Moreover, we found that MAPKAPK2 was exclusively localized in the cytoplasm in some neuronal cells under normal condition, suggesting that MAPKAPK2 is activated in these cells. It is possible that nuclear export (= cytoplasmic localization) of MAPKAPK2 is tightly associated with activation of
p38 MAPK and MAPKAPK2. We are currently examining when and where the
p38 MAPK/MAPKAPK2 pathway is functioning in living C. elegans by this method.