| 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.Unlike other RSK isoforms, the N-terminal region of RSK3 contains a putative nuclear localization signal and the kinase translocates to the nucleus in serum-starved HeLa cells. RSK3 is expressed ubiquitously in human tissues and localizes to developing neural and sensory areas in the mouse. Altered expression and mutations in the corresponding gene are associated with breast cancer and in some cancer cell lines, suggesting a possible role for this kinase as a tumor suppressor.
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