Inactive 90 kDa ribosomal S6 kinases (RSKs) can be detected in both the cytosol and the nucleus (Chen et al. 1992). Based on the available experimental evidence, it is most likely that activation of RSKs happens in the vicinity of the plasma membrane and that active RSKs then translocate to the nucleus (Chen et al. 1992, Smith et al. 1999, Richards et al. 2001, Murphy et al. 2002), but there is a possibility that activation of RSKs can also occur in the nucleus (Chen et al. 1992, reviewed in Anjum and Blenis 2012).