Nuclear protein NP60 regulates p38 MAPK activity

The activation of p38 is mediated by its upstream kinase and associated proteins. Here we identify a new nuclear protein, NP60, which regulates the activation of p38 in response to sorbitol treatment. NP60 specifically binds to p38, but not to JNK and ERK, in vitro and in vivo. Co-transfection of NP60 leads to the phosphorylation and activation of p38, and subsequently results in the phosphorylation and activation of activating transcription factor 2. The phosphorylation of p38 induced by NP60 requires upstream activity of p38 MAP kinase, MAP kinase kinase 6 (MKK6) or MKK4. Our results indicate that NP60 mediates stress activation of p38 and regulates p38 signaling in a specific way.