title: NF-kappaB couples protein kinase B/Akt signaling to distinct survival pathways and the regulation of lymphocyte homeostasis in vivo.
abstract: Protein kinase B (PKBalpha/Akt1) a PI3K-dependent serine-threonine kinase, promotes T cell viability in response to many stimuli and regulates homeostasis and autoimmune disease in vivo. To dissect the mechanisms by which PKB inhibits apoptosis, we have examined the pathways downstream of PKB that promote survival after cytokine withdrawal vs Fas-mediated death. Our studies show that PKB-mediated survival after cytokine withdrawal is independent of protein synthesis and the induction of NF-kappaB. In contrast, PKB requires de novo gene transcription by NF-kappaB to block apoptosis triggered by the Fas death receptor. Using gene-deficient and transgenic mouse models, we establish that NF-kappaB1, and not c-Rel, is the critical signaling molecule downstream of the PI3K-PTEN-PKB signaling axis that regulates lymphocyte homeostasis.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Jones
authors.forename: Sam D
authors.initials: SD
authors.lastname: Saibil
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Pun
authors.forename: Alisha R
authors.initials: AR
authors.lastname: Elford
authors.forename: Madeleine
authors.initials: M
authors.lastname: Bonnard
authors.forename: Marc
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Sudha
authors.initials: S
authors.lastname: Arya
authors.forename: Michael E
authors.initials: ME
authors.lastname: Parsons
authors.forename: Connie M
authors.initials: CM
authors.lastname: Krawczyk
authors.forename: Steve
authors.initials: S
authors.lastname: Gerondakis
authors.forename: Wen-Chen
authors.initials: WC
authors.lastname: Yeh
authors.forename: James R
authors.initials: JR
authors.lastname: Woodgett
authors.forename: Mark R
authors.initials: MR
authors.lastname: Boothby
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D016207:Cytokines; D006706:Homeostasis; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic; D019014:fas Receptor
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D019014:fas Receptor