Rsk1 is a member of a family of 90kDa ribosomal protein S6 kinases, which includes Rsk1, Rsk2 and Rsk3. These are broadly expressed serine / threonine protein kinases activated in response to mitogenic stimuli, including extracellular signal regulated protein kinases Erk1 and Erk2. Rsk1 is activated by MAPK in vitro and in vivo via phosphorylation. Active Rsks appear to play a major role in transcriptional regulation by translocating to the nucleus and phosphorylating c-Fos and CREB. RSK proteins possess two separate kinase domains, the C terminal kinase domain and the N terminal kinase domain, separated by a linker region containing a hydrophobic motif. RSK is activated by many stimuli including growth factors, phorbol esters, cAMP, heat shock, and irradiation.