Figure 2. Cytoplasmic localization of ADAR1p110 is regulated by p38 MAP kinase signaling.
(a) Various MAP kinase activating kinase expression constructs were co-transfected with mCherry-ADAR1p110-WT into A172 cells (left summary graph). Only MKK6* (constitutively active MKK6) significantly increased cytoplasmic localization of ADAR1p110 in UV un-irradiated A172 cells. Images of ∼30 cells each from (x02267)7 separate slides (n (x02267) 7) prepared independently (∼200 cells) were examined for mCherry-ADAR1p110 distribution between nucleus and cytoplasm. Data are mean ± S.D.; significant differences were identified by two-tailed Student's t-tests: ***P <0.001. Source data are available online in Source Data Set 1. The cytoplasmic localization was completely blocked by SB203580 (p38 inhibitor). (b) Phosphorylated p38 (pp38) localizes exclusively in the nucleus in UV irradiated A172 cells. The p38 inhibitor, although not affecting the nuclear localization of pp38, blocks the cytoplasmic localization of mCherry-ADAR1p110. (c) UV-irradiation induced cytoplasmic localization of mCherry-ADAR1p110-WT was blocked by simultaneous knockdown of MSK1 and MSK2. (a-c) Scale bars, 20 μm.