title: Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism.
abstract: In cytotoxic T cells (CTL), Akt, also known as protein kinase B, is activated by the T cell antigen receptor (TCR) and the cytokine interleukin 2 (IL-2). Akt can control cell metabolism in many cell types but whether this role is important for CTL function has not been determined. Here we have shown that Akt does not mediate IL-2- or TCR-induced cell metabolic responses; rather, this role is assumed by other Akt-related kinases. There is, however, a nonredundant role for sustained and strong activation of Akt in CTL to coordinate the TCR- and IL-2-induced transcriptional programs that control expression of key cytolytic effector molecules, adhesion molecules, and cytokine and chemokine receptors that distinguish effector versus memory and naive T cells. Akt is thus dispensable for metabolism, but the strength and duration of Akt activity dictates the CTL transcriptional program and determines CTL fate.
authors.affiliation: College of Life Sciences, Division of Cell Biology & Immunology, University of Dundee, Scotland, UK.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Macintyre
authors.forename: David
authors.initials: D
authors.lastname: Finlay
authors.forename: Gavin
authors.initials: G
authors.lastname: Preston
authors.forename: Linda V
authors.initials: LV
authors.lastname: Sinclair
authors.forename: Caryll M
authors.initials: CM
authors.lastname: Waugh
authors.forename: Peter
authors.initials: P
authors.lastname: Tamas
authors.forename: Carmen
authors.initials: C
authors.lastname: Feijoo
authors.forename: Klaus
authors.initials: K
authors.lastname: Okkenhaug
authors.forename: Doreen A
authors.initials: DA
authors.lastname: Cantrell
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D058534:Class I Phosphatidylinositol 3-Kinases; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010649:Phenylalanine / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D011799:Quinazolines / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000225:Adenine; D058534:Class I Phosphatidylinositol 3-Kinases; D005947:Glucose; D007371:Interferon-gamma; D007376:Interleukin-2; D010649:Phenylalanine; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D052899:Pore Forming Cytotoxic Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011799:Quinazolines; D011948:Receptors, Antigen, T-Cell; D018121:Receptors, Cytokine; C477872:IC 87114; C483886:perforin, mouse; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse