MAP kinases/ERKs (MAPK1 and MAPK3), activated downstream of RAS signaling, activate RSKs by phosphorylating conserved serine and threonine residues in the linker region and the C-terminal kinase domain (CTKD). In the linker region of RPS6KA1 (RSK1), ERKs phosphorylate threonine residue T359 and serine residue S363. In the CTKD of RPS6KA1, ERKs phosphorylate threonine residue T573 (Dalby et al. 1998, Roux et al. 2003).