Universität zu Köln

Dan, Han C., Ebbs, Aaron, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Van Dyke, Terry, Basseres, Daniela S. and Baldwin, Albert S. (2014). Akt-dependent Activation of mTORC1 Complex Involves Phosphorylation of mTOR (Mammalian Target of Rapamycin) by I kappa B Kinase alpha (IKK alpha). J. Biol. Chem., 289 (36). S. 25227 - 25241. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

The serine/threonine protein kinase Akt promotes cell survival, growth, and proliferation through phosphorylation of different downstream substrates. A key effector of Akt is the mammalian target of rapamycin (mTOR). Akt is known to stimulate mTORC1 activity through phosphorylation of tuberous sclerosis complex 2 (TSC2) and PRAS40, both negative regulators of mTOR activity. We previously reported that I kappa B kinase alpha (IKK alpha), a component of the kinase complex that leads to NF-kappa B activation, plays an important role in promoting mTORC1 activity downstream of activated Akt. Here, we demonstrate IKK alpha-dependent regulation of mTORC1 using multiple PTEN null cancer cell lines and an animal model with deletion of IKK alpha. Importantly, IKK alpha is shown to phosphorylate mTOR at serine 1415 in a manner dependent on Akt to promote mTORC1 activity. These results demonstrate that IKK alpha is an effector of Akt in promoting mTORC1 activity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dan, Han C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ebbs, Aaron UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Van Dyke, Terry UNSPECIFIED UNSPECIFIED UNSPECIFIED Basseres, Daniela S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldwin, Albert S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-428943
DOI:	10.1074/jbc.M114.554881
Journal or Publication Title:	J. Biol. Chem.
Volume:	289
Number:	36
Page Range:	S. 25227 - 25241
Date:	2014
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-GROWTH; DOMAIN PHOSPHORYLATION; FEEDBACK INHIBITION; GENETIC-ANALYSIS; CANCER; PTEN; RHEB; TUMORIGENESIS; SUPPRESSION; BETA Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/42894