Glycogen synthase kinase (GSK)-3 promotes p70 ribosomal protein S6 kinase (p70S6K) activity and cell proliferation Academic Article uri icon


MeSH Major

  • Cell Proliferation
  • Glycogen Synthase Kinase 3
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases


  • The p70 ribosomal protein S6 kinase 1 (S6K1) plays a key role in cell growth and proliferation by regulating insulin sensitivity, metabolism, protein synthesis, and cell cycle. Thus, deregulation of S6K contributes to the progression of type 2 diabetes, obesity, aging, and cancer. Considering the biological and clinical importance of S6K1, a complete understanding of its regulation is critical. One of the key motifs in the activation of S6K1 is a turn motif, but its regulation is not well understood. Here we provide evidence for two mechanisms of modulating turn motif phosphorylation and S6K1 activity. First, mammalian target of rapamycin regulates turn motif phosphorylation by inhibiting its dephosphorylation. Second, we unexpectedly found that glycogen synthase kinase (GSK)-3 promotes turn motif phosphorylation. Our studies show that mammalian target of rapamycin and GSK-3 cooperate to control the activity of S6K1, an important regulator of cell proliferation and growth. Our unexpected results provide a clear rationale for the development and use of drugs targeting GSK-3 to treat diseases such as diabetes, cancer, and age-related diseases that are linked to improper regulation of S6K1.

publication date

  • November 22, 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3223461

Digital Object Identifier (DOI)

  • 10.1073/pnas.1110195108

PubMed ID

  • 22065737

Additional Document Info

start page

  • E1204

end page

  • 13


  • 108


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