Figure 3.

Illustration of RSK2 activation mechanisms. The activated extracellular signal-regulated kinase (ERK) binds at the ERK docking consensus sequences in the C-terminal domain of RSK2 and phosphorylates at Thr365/Ser369 in the linker domain and at Thr577 in the C-terminal kinase domain (CTKD), resulting in the activation of CTKD. The activated CTKD then phosphorylates at Ser386 in the linker domain, providing a docking site for PDK1. The PDK1 phosphorylates at Ser227 in the N-terminal kinase domain (NTKD), resulting in the activation of NTKD. The activated NTKD obtains ability to phosphorylate the downstream target proteins, which include kinases, transcription factors, and epigenetic factors.