Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis.
Proper regulation of the phosphoinositide 3-kinase-Akt pathway is critical for the prevention of both insulin resistance and tumorigenesis. Many recent studies have characterized a negative feedback loop in which components of one downstream branch of this pathway, composed of the mammalian target of rapamycin and ribosomal S6 kinase, block further activation of the pathway through inhibition of insulin receptor substrate function. These findings form a novel basis for improved understanding of the pathophysiology of metabolic diseases (e.g., diabetes and obesity), tumor syndromes (e.g., tuberous sclerosis complex and Peutz-Jegher's syndrome), and human cancers.
Manning
Brendan D
BD
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA. bmanning@hsph.harvard.edu
D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance; D008659:Metabolic Diseases / Q000209:etiology; D009369:Neoplasms / Q000209:etiology; D011494:Protein Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448959:ribosomal protein S6 kinase, 70kD, polypeptide 2