Anti-RSK2: Mouse RSK2 Antibody Product

The precise mechanism of RSK activation remains elusive. The current model suggests that following mitogen stimulation, ERK phosphorylates RSK1 Thr590 (according to avian RSK1 numbering; human 573), located in the activation loop of the C-terminal kinase domain, and possibly Ser381 (turn motif; human 363) and Thr377 (human 359) in the linker region between the two kinase domains. Activation of RSK1 is absolutely dependent on ERK docking near the C terminus of RSK1. Activation of the C-terminal kinase domain leads to autophosphorylation of Ser398 (hydrophobic motif; human 380), also located in the linker region. This creates a docking site for PDK1, which then phosphorylates Ser239 (human 221) in the activation loop of the N-terminal kinase domain, allowing RSK to phosphorylate all its targets.⁴ Interestingly, Ser749 (human 732) is located near the ERK docking site and represents another mitogen-regulated phosphorylation site in RSK1. This residue is thought to be regulated by autophosphorylation from the N-terminal kinase domain, as it fits a RSK consensus phosphorylation sequence (K/RXXS/T). Ser749 phosphorylation regulates interaction between ERK1/2 and RSK1. Moreover, mutations that affect RSK1 kinase activity prevent ERK1/2 dissociation from RSK1 following mitogen stimulation in vivo. Analysis of different RSK isoforms revealed that RSK1 and RSK2 dissociate from ERK1/2 following mitogen stimulation but that RSK3 remains associated with active ERK1/2. ERK dissociation from RSK1 and RSK2 correlated with shorter duration of activity compared to RSK3, indicating that ERK dissociation may shorten RSK activation.⁵