Ribosomal Protein S6 Kinase 90kDa Polypeptide 3, CLS, EC=2.7.11.1, HU-3, MRX19, RSK

Members of the RSK (the p90 ribosomal S6 kinase) family of serine/threonine kinases are substrates of ERK (the Ras/extracellular signal-regulated kinase) (1). The RSK family consists of four isoforms (RSK1 to -4) and two structurally related cousins, called RSK-like protein kinase (RLPK/MSK1) and RSKB (MSK2). RSK2 is expressed in most tissues including heart, brain, placenta, liver, kidney and pancreas, with predominant expression in skeletal muscle (4-5). The small death effector domain protein PEA-15 inhibits RSK2 nuclear translocation, but the biological function of this interaction is unknown6. Activated RSK2 can also be found in the cytoplasm of stimulated cells suggesting that RSK2 substrates may exist in both nuclear and cytoplasmic compartments (7). A phosphate-binding pocket in the kinase domain of RSK2 is used for intramolecular interaction with its own phosphorylated hydrophobic motif, an interaction that induces a synergistic stimulation of RSK2 catalytic activity, whereas mutation of the phosphate-binding pocket leads to a reduction in the overall kinase activity of RSK28. Defects in the RSK2 gene are the cause of Coffin-Lowry syndrome, an X-linked dominant disorder characterized by psychomotor and growth retardation and facial, hand and skeletal malformations9-10. Numerous mutations have been identified in the RSK2 gene that result in truncated or inactive RSK2 proteins (11-12).