title: Phosphorylation of Akt at the C-terminal tail triggers Akt activation.
abstract: Aberrant hyper-activation of the protein kinase Akt plays a critical role in promoting tumorigenesis. Mechanistically, previous studies establish that phosphorylation of Akt at S473 and T308 by mTORC2 and PDK1, respectively, is necessary for its full activation, thereby having been used as Akt activation markers. Recently, we report that phosphorylation of S477 and T479 at the extreme C-terminus of Akt1 promotes Akt1 activation. We further demonstrate that Akt1 pS477 and pT479 events are governed by Cdk2/Cyclin A or mTORC2 under distinct cellular contexts such as cell cycle progression or growth stimulation conditions. Here, we summarize our major findings regarding the biological significance for pS477/pT479-mediated activation of Akt and also provide perspectives for future follow-up studies.
authors.affiliation: Department of Pathology; Beth Israel Deaconess Medical Center; Harvard Medical School; Boston, MA USA.
authors.forename: Pengda
authors.initials: P
authors.lastname: Liu
authors.affiliation: The Cyrus Tang Hematology Center; Jiangsu Institute of Hematology; The First Affiliated Hospital; Soochow University; Suzhou, PR China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology; Beth Israel Deaconess Medical Center; Harvard Medical School; Boston, MA USA.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D006801:Humans; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; C089212:protein kinase D; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C
keywords: Cancer signaling; Cdk2/Cyclin A; mTOR/Akt pathway; mTORC2; phosphorylation; protein kinase