This entry represents the C-terminal catalytic domain of ribosomal protein S6 kinase alpha-3.RPS6KA3 (also called RSK2) is expressed highly in the regions of the brain with high synaptic activity and plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis []. Mutations in the RPS6KA3 gene cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterised by growth and psychomotor retardation and skeletal abnormalities []. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates.The most striking feature of RSKs is the presence of two functional and non-identical phosphotransferase domains []. RSKs contain an N-terminal kinase domain (NTD) that is characteristics of the AGC family and a C-terminal kinase domain (CTD) that is characteristics of the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival [, , ].
