title: Deconvolution of mTORC2 "in Silico".
abstract: The protein kinase mTOR (mammalian or mechanistic target of rapamycin) coordinates a complex signal transduction network. By assembling with unique and shared partner proteins, mTOR forms the catalytic core of at least two complexes, mTOR complex 1 (mTORC1) and mTORC2, that show differential sensitivity to the allosteric mTOR inhibitor rapamycin and that phosphorylate distinct substrates to modulate cell growth, proliferation, survival, and metabolism in response to diverse environmental cues. Understanding mTOR network circuitry will provide insight into how its deregulation contributes to pathologic states such as diabetes, cancer, and cardiovascular disease. Research published in Science Signaling describes an investigation of the complex insulin-mTOR network by combining classic biochemical approaches with dynamic mathematical modeling in silico to elucidate how insulin activates mTORC2, an event that remains poorly defined.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. dfingar@umich.edu
authors.forename: Diane C
authors.initials: DC
authors.lastname: Fingar
authors.forename: Ken
authors.initials: K
authors.lastname: Inoki
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D003198:Computer Simulation; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012984:Software; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D007328:Insulin; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; D058570:TOR Serine-Threonine Kinases