Functions and regulation of the 70kDa ribosomal S6 kinases

• Published in: The international journal of biochemistry & cell biology Vol. 43; no. 1; pp. 47 - 59
• Main Authors: Fenton, Tim R, Gout, Ivan T
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 2011
• Subjects: Animals; business enterprises; Cell Cycle - drug effects; cell growth; Cell Line; Cellular Senescence; cytokines; diabetes; Drosophila; Enzyme Activation; Female; Gene Expression Regulation, Enzymologic - physiology; glucose; growth factors; homeostasis; human diseases; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; messenger RNA; Mice; nutrients; obesity; pathogenesis; patients; Phosphorylation - drug effects; Protein Biosynthesis - drug effects; Protein Kinase Inhibitors - pharmacology; Protein Structure, Tertiary; protein synthesis; protein-serine-threonine kinases; Ribosomal Protein S6 Kinases, 70-kDa - antagonists & inhibitors; Ribosomal Protein S6 Kinases, 70-kDa - genetics; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors; Ribosomal Protein S6 Kinases, 90-kDa - genetics; Ribosomal Protein S6 Kinases, 90-kDa - metabolism; Ribosomes - enzymology; Ribosomes - metabolism; signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology; Substrate Specificity - physiology
• ISSN: 1357-2725; 1878-5875; 1878-5875
• DOI: 10.1016/j.biocel.2010.09.018

The 70kDa ribosomal protein S6 kinases, S6K1 and S6K2 are two highly homologous serine/threonine kinases that are activated in response to growth factors, cytokines and nutrients. The S6 kinases have been linked to diverse cellular processes, including protein synthesis, mRNA processing, glucose homeostasis, cell growth and survival. Studies in model organisms have highlighted the roles that S6K activity plays in a number of pathologies, including obesity, diabetes, ageing and cancer. The importance of S6K function in human diseases has led to the development of S6K-specific inhibitors by a number of companies, offering the promise of improved tools with which to study these enzymes and potentially the effective targeting of deregulated S6K signalling in patients. Here we review the current literature on the role of S6Ks in the regulation of cell growth, survival and proliferation downstream of various signalling pathways and how their dysregulation contributes to the pathogenesis of human diseases.