Ser/Thr phosphorylation of IRS proteins: a molecular basis for insulin resistance.
S6K1, like other serine and threonine kinases activated by insulin (such as mTOR and PKCzeta), has recently been shown to participate in negative feedback mechanisms aimed at terminating insulin signaling through IRS (insulin receptor substrate) phosphorylation. Such homeostatic mechanisms can also be activated by excess nutrients or inducers of insulin resistance (such as fatty acids and proinflammatory cytokines) to produce an insulin-resistant state that often leads to the development of diabetes. Identification of the specific kinases involved in such insulin resistance pathways can help lead to the rational design of novel therapeutic agents for treating insulin resistance and type 2 diabetes.
Zick
Yehiel
Y
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. yehiel.zick@weizmann.ac.il <yehiel.zick@weizmann.ac.il>
D000818:Animals; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D025461:Feedback, Physiological; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology / Q000503:physiopathology; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011972:Receptor, Insulin / Q000502:physiology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D000099221:Protein Kinase C zeta
D016207:Cytokines; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D010750:Phosphoproteins; D011493:Protein Kinase C; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011972:Receptor, Insulin; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D000099221:Protein Kinase C zeta; C546842:MTOR protein, human; C546843:mTOR protein, mouse; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1