2011
DOI: 10.1073/pnas.1110195108
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Glycogen synthase kinase (GSK)-3 promotes p70 ribosomal protein S6 kinase (p70S6K) activity and cell proliferation

Abstract: 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 p… Show more

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Cited by 155 publications
(139 citation statements)
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“…As shown in Fig. 8D, GSK3␤ directly activates p70 ribosomal protein S6 kinase (p70S6K), a downstream target of mTORC1 (48). Reciprocally, p70S6K phosphorylates and then inactivates GSK3␤, indicating a negative feedback loop.…”
Section: Discussionmentioning
confidence: 99%
“…As shown in Fig. 8D, GSK3␤ directly activates p70 ribosomal protein S6 kinase (p70S6K), a downstream target of mTORC1 (48). Reciprocally, p70S6K phosphorylates and then inactivates GSK3␤, indicating a negative feedback loop.…”
Section: Discussionmentioning
confidence: 99%
“…1). 6 Although GSK-3β was first identified as an enzyme that regulates glycogen metabolism by modulating glycogen synthase, intensive studies have revealed that GSK-3β is involved in a variety of physiological processes including glucose homeostasis, insulin signaling, neurodevelopmental processes, immune response and inflammation. Therefore, dysregulation of GSK-3β is involved in metabolic diseases, such as type 2 diabetes, neurological disorders such as Alzheimer disease and Parkinson disease, and autoimmune diseases.…”
mentioning
confidence: 99%
“…For example, GSK-3β has been shown to regulate nuclear factor κB (NFκB), Notch signaling, tumor-suppressor protein p53, oncoprotein Maf and homeobox (HOX) genes. 6 In addition, a recent kinome-wide screen demonstrated that GSK-3 is a positive regulator of Akt, a key player in cancer cell survival and proliferation. 9 In addition to a direct role in cancer, GSK-3β can also indirectly promote cancer progression.…”
mentioning
confidence: 99%
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