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

Sejeong Shin, Laura Wolgamott, Yonghao Yu, John Blenis, Sang Oh Yoon

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130 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)E1204-E1213
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number47
StatePublished - Nov 22 2011

ASJC Scopus subject areas

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