title: Phosphorylation of AKT: a mutational analysis.
abstract: Akt (cellular homolog of murine thymoma virus akt8 oncogene) is an essential component of the PI3K (phosphatidylinositol 3-kinase) pathway. Its activity is stimulated by receptor tyrosine kinases and G-protein coupled receptors and plays a critical role in the regulation of cell proliferation, differentiation and apoptosis. A gain of function in Akt can lead to uncontrolled cell proliferation and resistance to apoptosis, both hallmarks of oncogenic transformation. In this communication, we have investigated the phosphorylation at the Akt residues T308, S473 and T450 and their roles in oncogenic transformation and signaling. We find that T450 phosphorylation has only a minimal part in these activities. In contrast, the phosphorylation of T308 and of S473 fulfills essential, distinct, and non-overlapping functions that we define with inactivating and with phosphomimetic mutations of these sites.
authors.affiliation: The Scripps Research Institute, Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. jhart@scripps.edu
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Hart
authors.forename: Peter K
authors.initials: PK
authors.lastname: Vogt
mesh_terms: D000818:Animals; D020134:Catalytic Domain / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D004252:DNA Mutational Analysis; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt