| Background |
The 90 kDa ribosomal S6 kinases (RSK1-4) are a family of widely expressed Ser/Thr kinases characterized by two nonidentical, functional kinase domains and a carboxy-terminal docking site for extracellular signal-regulated kinases (ERKs). Several sites both within and outside of the RSK kinase domain, including Ser380, Thr359, Ser363, and Thr573, are important for kinase activation. RSK1-3 are activated via coordinated phosphorylation by MAPKs, autophosphorylation, and phosphoinositide-3-OH kinase (PI3K) in response to many growth factors, polypeptide hormones, and neurotransmitters.PDK1 phosphorylates Ser227 in the activation loop of the amino-terminal kinase domain of RSK2, leading to substantial activation of the kinase in vitro and in vivo. The constitutively active PDK1 cooperates with ERK in the activation of RSK following the exposure of cells to growth factors or UV-light.
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