Function: Serine/threonine kinase that may play a role in mediating the growth-factor and stress induced activation of the transcription factor CREB. Tissue specificity: Expressed in many tissues, highest levels in skeletal muscle. Disease: Defects in RPS6KA3 are the cause of Coffin-Lowry syndrome (CLS) [MIM:303600]; an X-linked dominant disorder characterized by severe mental retardation with facial and digital dysmorphisms, and progressive skeletal deformations. Similarity: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 2 protein kinase domains. PTM: Autophosphorylated on Ser-386, as part of the activation process. Ser-227 phosphorylation promotes Ser-386 phosphorylation and leads to basal activation. Full activation by growth factors requires additional phosphorylation on Ser-369.