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Previously, we showed that activation of mTOR in PTEN-deficient cancer cells involves I\u03baB kinase (IKK) \u03b1, a catalytic subunit of the IKK complex that controls NF-\u03baB activation. Recently, a distinct IKK subunit, IKK\u03b2, was shown to phosphorylate TSC1 to promote mTOR activation in an Akt-independent manner in certain cells stimulated with TNF and in some cancer cells. In this study, we have explored the involvement of both IKK\u03b1 and IKK\u03b2 in insulin- and TNF-induced mTOR activation. Insulin activation of mTOR requires Akt in a manner that involves IKK\u03b1, preferentially to IKK\u03b2, and TSC2 phosphorylation. TNF, in most cells examined, activates Akt to use IKK\u03b1 to control mTOR activation. In MCF7 cells, TNF does not activate Akt and requires IKK\u03b2 to activate mTOR. The results show that Akt-dependent signaling, induced by cytokines or insulin, alters the IKK subunit-dependent control of mTOR.<\/jats:p>","DOI":"10.4049\/jimmunol.180.11.7582","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:09:57Z","timestamp":1397848197000},"page":"7582-7589","source":"Crossref","is-referenced-by-count":66,"title":["Differential Involvement of I\u03baB Kinases \u03b1 and \u03b2 in Cytokine- and Insulin-Induced Mammalian Target of Rapamycin Activation Determined by Akt"],"prefix":"10.1093","volume":"180","author":[{"given":"Han C","family":"Dan","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert S","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,6,1]]},"reference":[{"key":"2026012809145881400_R1","first-page":"6361","volume-title":"Oncogene","year":"2006"},{"key":"2026012809145881400_R2","first-page":"3151","volume-title":"Oncogene","year":"2004"},{"key":"2026012809145881400_R3","first-page":"1926","volume-title":"Genes Dev.","year":"2004"},{"key":"2026012809145881400_R4","first-page":"471","volume-title":"Cell","year":"2006"},{"key":"2026012809145881400_R5","first-page":"1165","volume-title":"Cell Death Differ.","year":"2001"},{"key":"2026012809145881400_R6","first-page":"440","volume-title":"Cell","year":"2007"},{"key":"2026012809145881400_R7","first-page":"4640","volume-title":"Proc. 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