The family of ribosomal S6 kinases (Rsks), designated Rsk-1 (MAPKAP kinase-1), Rsk-2 and Rsk-3, are intracellular serine/threonine kinases that are important signaling intermediates in response to a broad range of ligand activated receptor tyrosine kinases. A unique feature common to the members of the Rsk family is that each possesses two non-identical complete kinase catalytic domains. An additional Rsk protein, Rsk-4, shows a high level of homology to the three previously isolated members of the human Rsk family. Rsk-4 is most abundantly expressed in brain and kidney and plays a role in normal neuronal development. The 70 kDa family of ribosomal S6 kinases includes p70 S6 kinase and p70 S6 kinase β, which are thought to have similar regulatory functions. MSK1 (also designated RLPK) is a novel Rskrelated protein, which, like the p90 Rsk family members, contains two non-identical complete kinase catalytic domains.