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Science 24 October 1997:
Vol. 278. no. 5338, pp. 687 - 689
DOI: 10.1126/science.278.5338.687
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Reports

Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt

Luis del Peso, Maribel González-García, Carmen Page, Román Herrera, Gabriel Nuñez *

BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this. BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase-dependent manner. Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3. Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway.

L. del Peso, M. González-García, C. Page, G. Nuñez, Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
R. Herrera, Department of Signal Transduction, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105, USA.
*   To whom correspondence should be addressed. E-mail: Gabriel.Nunez{at}umich.edu

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Diverse Antiapoptotic Signaling Pathways Activated by Vasoactive Intestinal Polypeptide, Epidermal Growth Factor, and Phosphatidylinositol 3-Kinase in Prostate Cancer Cells Converge on BAD.
K. S. R. Sastry, A. J. Smith, Y. Karpova, S. R. Datta, and G. Kulik (2006)
J. Biol. Chem. 281, 20891-20901
   Abstract »    Full Text »    PDF »
Phosphatidylinositol-3-phosphate kinase pathway activation protects leukemic large granular lymphocytes from undergoing homeostatic apoptosis.
A. E. Schade, J. J. Powers, M. W. Wlodarski, and J. P. Maciejewski (2006)
Blood 107, 4834-4840
   Abstract »    Full Text »    PDF »
Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways..
D Sharma, N K Saxena, P M Vertino, and F A Anania (2006)
Endocr. Relat. Cancer 13, 629-640
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-kinase improves the efficiency of positive selection.
S. D Barbee and J. Alberola-Ila (2006)
Int. Immunol. 18, 921-930
   Abstract »    Full Text »    PDF »
Inhibition of Akt by the alkylphospholipid perifosine does not enhance the radiosensitivity of human glioma cells..
L. de la Pena, W. E. Burgan, D. J. Carter, M. G. Hollingshead, M. Satyamitra, K. Camphausen, and P. J. Tofilon (2006)
Mol. Cancer Ther. 5, 1504-1510
   Abstract »    Full Text »    PDF »
Protein Kinase C-{theta}-Mediated Signals Enhance CD4+ T Cell Survival by Up-Regulating Bcl-xL..
S. Manicassamy, S. Gupta, Z. Huang, and Z. Sun (2006)
J. Immunol. 176, 6709-6716
   Abstract »    Full Text »    PDF »
Therapeutic Effect of Imatinib in Gastrointestinal Stromal Tumors: AKT Signaling Dependent and Independent Mechanisms..
C. Tarn, Y. V. Skorobogatko, T. Taguchi, B. Eisenberg, M. von Mehren, and A. K. Godwin (2006)
Cancer Res. 66, 5477-5486
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Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis.
L. Kim and E. Y. Denkers (2006)
J. Cell Sci. 119, 2119-2126
   Abstract »    Full Text »    PDF »
Akt Binds to and Phosphorylates Phospholipase C-{gamma}1 in Response to Epidermal Growth Factor.
Y. Wang, J. Wu, and Z. Wang (2006)
Mol. Biol. Cell 17, 2267-2277
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Basic fibroblast growth factor protects against rotenone-induced dopaminergic cell death through activation of extracellular signal-regulated kinases 1/2 and phosphatidylinositol-3 kinase pathways..
S.-L. Hsuan, H. M. Klintworth, and Z. Xia (2006)
J. Neurosci. 26, 4481-4491
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Varicella-zoster virus influences the activities of components and targets of the ERK signalling pathway..
M. Rahaus, N. Desloges, and M. H. Wolff (2006)
J. Gen. Virol. 87, 749-758
   Abstract »    Full Text »    PDF »
Inactivation of the Akt Survival Pathway during Photoreceptor Apoptosis in the Retinal Degeneration Mouse..
C. Jomary, J. Cullen, and S. E. Jones (2006)
Invest. Ophthalmol. Vis. Sci. 47, 1620-1629
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Immortalization of Primary Endothelial Cells by the K1 Protein of Kaposi's Sarcoma-Associated Herpesvirus..
L. Wang, D. P. Dittmer, C. C. Tomlinson, F. D. Fakhari, and B. Damania (2006)
Cancer Res. 66, 3658-3666
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Maintenance of Bad Phosphorylation Prevents Apoptosis of Rat Hepatic Sinusoidal Endothelial Cells in Vitro and in Vivo.
N. Ohi, Y. Nishikawa, T. Tokairin, Y. Yamamoto, Y. Doi, Y. Omori, and K. Enomoto (2006)
Am. J. Pathol. 168, 1097-1106
   Abstract »    Full Text »    PDF »
A Novel Neuroprotectant Granulocyte-Colony Stimulating Factor.
I. Solaroglu, J. Cahill, V. Jadhav, and J. H. Zhang (2006)
Stroke 37, 1123-1128
   Abstract »    Full Text »    PDF »
Antianoikis Effect of Nuclear Factor-{kappa}B through Up-regulated Expression of Osteoprotegerin, BCL-2, and IAP-1.
M. Toruner, M. Fernandez-Zapico, J. J. Sha, L. Pham, R. Urrutia, and L. J. Egan (2006)
J. Biol. Chem. 281, 8686-8696
   Abstract »    Full Text »    PDF »


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