TY - JOUR
T1 - Induction of NF-κB by the Akt/PKB kinase
AU - Kane, Lawrence P.
AU - Shapiro, Virginia Smith
AU - Stokoe, David
AU - Weiss, Arthur
N1 - Funding Information:
We thank the following investigators for providing reagents: A. Baldwin, D. Ballard, J. Didonato, J. Downward, D. Goeddel, W. Greene, and D. Wallach. We also thank T. Finco and M. Kuhne for critical reading of the manuscript, and X. Lin, R. Geleziunas, and W. Greene for sharing data before publication. L.P.K. is supported by a training grant from the NIH to the Rheumatology division. V.S.S. is a Leukemia Society of America Special Fellow. A.W. is supported by The Howard Hughes Medical Institute.
PY - 1999/6/3
Y1 - 1999/6/3
N2 - The serine/threonine kinase Akt (also known as protein kinase B, PKB) is activated by numerous growth-factor and immune receptors through lipid products of phosphatidylinositol (PI) 3-kinase. Akt can couple to pathways that regulate glucose metabolism or cell survival. Akt can also regulate several transcription factors, including E2F, CREB, and the Forkhead family member Daf-16. Here, we show that Akt can regulate signaling pathways that lead to induction of the NF-κB family of transcription factors in the Jurkat T-cell line. This induction occurs, at least in part, at the level of degradation of the NF-κB inhibitor IκB, and is specific for NF-κB, as other inducible transcription factors are not affected by Akt overexpression. Furthermore, the effect requires the kinase activity and pleckstrin homology (PH) domain of Akt. Also, Akt does not act alone to induce cytokine promoters and NF-κB reporters, because signals from other pathways are required to observe the effect. These studies uncover a previously unappreciated connection between Akt and NF-κB induction that could have implications for the control of T-cell growth and survival.
AB - The serine/threonine kinase Akt (also known as protein kinase B, PKB) is activated by numerous growth-factor and immune receptors through lipid products of phosphatidylinositol (PI) 3-kinase. Akt can couple to pathways that regulate glucose metabolism or cell survival. Akt can also regulate several transcription factors, including E2F, CREB, and the Forkhead family member Daf-16. Here, we show that Akt can regulate signaling pathways that lead to induction of the NF-κB family of transcription factors in the Jurkat T-cell line. This induction occurs, at least in part, at the level of degradation of the NF-κB inhibitor IκB, and is specific for NF-κB, as other inducible transcription factors are not affected by Akt overexpression. Furthermore, the effect requires the kinase activity and pleckstrin homology (PH) domain of Akt. Also, Akt does not act alone to induce cytokine promoters and NF-κB reporters, because signals from other pathways are required to observe the effect. These studies uncover a previously unappreciated connection between Akt and NF-κB induction that could have implications for the control of T-cell growth and survival.
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U2 - 10.1016/S0960-9822(99)80265-6
DO - 10.1016/S0960-9822(99)80265-6
M3 - Article
C2 - 10359702
AN - SCOPUS:0033519453
SN - 0960-9822
VL - 9
SP - 601
EP - 604
JO - Current Biology
JF - Current Biology
IS - 11
ER -