| 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.PI3K-induced activation of RSK1 is mediated by the Ser/Thr kinase mTOR (mammalian target of rapamycin). This activation of RSK1 selectively increases the translation of mRNA transcripts containing a tract of pyrimidine (TOP) motif. An association between RSK1 and specific PKA subunits depends upon RSK1 activation state and determines both intracellular localization and specific activity of the kinase. Evidence from animal models suggests that RSK1 is a key regulator of glucose homeostasis and cell size.
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