RSK2/A0268

RPS6KA3 (Ribosomal protein S6 kinase alpha-3, Ribosomal S6 kinase 2, RSK2), also known as A0268, is a member of the RSK family of serine/threonine kinases.

RPS6KA3 (Ribosomal protein S6 kinase alpha-3, Ribosomal S6 kinase 2, RSK2), also known as A0268, is a member of the RSK family of serine/threonine kinases. This kinase contains two non-identical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated protein kinase (MAPK) signaling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. RSK genes express in various human tissues, during mouse embryogenesis and in the mouse brain. In the adult mouse brain, the highest levels of RSK2 expression is in regions with high synaptic activity, including the neocortex, the hippocampus and Purkinje cells, therefore suggesting that in these areas, which are essential to cognitive function and learning, the RSK1 and RSK3 genes may not be able to fully compensate for a lack of RSK2 function. Mice with a null mutation for RSK2 showed that RSK2 is required for osteoblast differentiation and function. In the rat brain, RSK2 binds PDZ domain proteins. Mutation of the RSK2 PDZ ligand greatly reduces RSK2 phosphorylation of PDZ domains of the Shank family of proteins in heterologous cells. In primary neurons, N-methyl-D-aspartate (NMDA) receptor activation leads to extracellular signal-regulated kinase (ERK) and RSK2 activation and RSK-dependent phosphorylation of transfected SHANK3, thereby suggesting that binding of RSK2 to PDZ domain proteins and phosphorylation of these proteins regulates excitatory synaptic transmission. Mutations in the human RSK2 gene have been associated with Coffin-Lowry syndrome (CLS).