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Interleukin 3-dependent survival by the Akt protein kinase

Songyang, Zhou and Baltimore, David and Cantley, Lewis C. and Kaplan, David R. and Franke, Thomas F. (1997) Interleukin 3-dependent survival by the Akt protein kinase. Proceedings of the National Academy of Sciences of the United States of America, 94 (21). pp. 11345-11350. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:SONpnas97

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Abstract

Interleukin 3 (IL-3)-dependent survival of hematopoietic cells is known to rely on the activity of multiple signaling pathways, including a pathway leading to activation of phosphoinositide 3-kinase (PI 3-kinase), and protein kinase Akt is a direct target of PI 3-kinase. We find that Akt kinase activity is rapidly induced by the cytokine IL-3, suggesting a role for Akt in PI 3-kinase-dependent signaling in hematopoetic cells. Dominant-negative mutants of Akt specifically block Akt activation by IL-3 and interfere with IL-3-dependent proliferation. Overexpression of Akt or oncogenic v-akt protects 32D cells from apoptosis induced by IL-3 withdrawal. Apoptosis after IL-3 withdrawal is accelerated by expression of dominant-negative mutants of Akt, indicating that a functional Akt signaling pathway is necessary for cell survival mediated by the cytokine IL-3. Thus Akt appears to be an important mediator of anti-apoptotic signaling in this system.


Item Type:Article
Additional Information:Copyright © 1997 by the National Academy of Sciences. Contributed by David Baltimore, August 12, 1997. We thank M. Boudreau, H. Chang, R. Friedrich, A. Kazlauskas, R. Khosravi-Far, G. Thomas, and X. Yang for critical reading of the manuscript. This work was supported by Public Health Service Grants CA51962 (D.B.) and GM41890 (L.C.C.) and by the National Cancer Institute of Canada (D.R.K.). Z.S. is a recipient of the Irvington Institute Fellowship. T.F.F. is a recipient of the K.M. Hunter Fellowship in Cancer Research from the National Cancer Institute of Canada supported with funds provided by the Terry Fox Run. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE 5-PHOSPHATASE, INOSITOL POLYPHOSPHATE 5-PHOSPHATASE, COLONY-STIMULATING FACTOR, HEMATOPOIETIC-CELLS, SIGNAL-TRANSDUCTION, C-AKT, MULTIPLE CYTOKINES, MOLECULAR-CLONING, V-AKT, ACTIVATION
Record Number:CaltechAUTHORS:SONpnas97
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:SONpnas97
Alternative URL:http://www.pnas.org/cgi/content/abstract/94/21/11345
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:885
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Nov 2005
Last Modified:26 Dec 2012 08:41

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