SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2002-04-1251. This Article Full Text (PDF) All Versions of this Article: 2002-04-1251v1 101/1/236    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jiang, K. Articles by Djeu, J. Y Search for Related Content PubMed PubMed Citation Articles by Jiang, K. Articles by Djeu, J. Y Social Bookmarking                   What's this? Submitted April 29, 2002 Accepted August 7, 2002 Regulation of AKT dependent cell survival by Syk and Rac Kun Jiang, Bin Zhong, Connie Ritchey, Danielle L Gilvary, Elizabeth Hong-Geller, Sheng Wei, and Julie Y Djeu* Immunology Program, H. Lee Moffitt Cancer, Tampa, FL, USA Los Alamos National Laboratories, Los Alamos, NM, USA * Corresponding author; email: djeu{at}moffitt.usf.edu. IL2 prevents cell apoptosis and promotes survival but the involved mechanisms have not been completely defined. Although PI 3-kinase has been implicated in IL2- mediated survival mechanisms, none of the three chains of the IL2 receptor (IL2R) expresses a binding site for PI 3-kinase. However, IL2Rb does express a Syk-binding motif. By utilizing an IL2-dependent natural killer (NK) cell line, followed by validation of the results in fresh human NK cells, we identified Syk as a critical effector essential for IL2-mediated prosurvival signaling in NK cells. Down-regulation of Syk by piceatannol treatment impaired NK cellular viability and induced prominent apoptosis as effectively as suppression of PI 3-kinase function by LY294002. Expression of kinase-deficient Syk or pretreatment with piceatannol markedly suppressed IL2-stimulated activation of PI 3-kinase and AKT, demonstrating that Syk is upstream of PI 3-kinase and AKT. However, constitutively active PI 3-kinase reversed this loss of AKT function caused by kinase-deficient Syk or piceatannol. Thus, Syk appears to regulate PI 3-kinase which controls AKT activity during IL2-stimulation. More importantly, we observed Rac1 activation by IL2 and found that it mediated PI 3-kinase activation of AKT. This conclusion came from experiments where dominant-negative Rac1 significantly decreased IL2-induced AKT activation while constitutively-active Rac1 re-elevated AKT activity in not only Syk- but also PI 3-kinase-impaired NK cells. These results constitute the first report of a SykPI3KRac1AKT signal cascade controlled by IL2 that mediates NK cell survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. P. Fortin, M. J. Ennis, B. A. Savitch, D. Carpentieri, W. S. McDonough, J. A. Winkles, J. C. Loftus, C. Kingsley, G. Hostetter, and N. L. Tran Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Stimulation of Glioma Cell Survival Is Dependent on Akt2 Function Mol. Cancer Res., November 1, 2009; 7(11): 1871 - 1881. [Abstract] [Full Text] [PDF] M. S. Turner, L. P. Kane, and P. A. Morel Dominant Role of Antigen Dose in CD4+Foxp3+ Regulatory T Cell Induction and Expansion J. Immunol., October 15, 2009; 183(8): 4895 - 4903. [Abstract] [Full Text] [PDF] E. Zebedin, O. Simma, C. Schuster, E. M. Putz, S. Fajmann, W. Warsch, E. Eckelhart, D. Stoiber, E. Weisz, J. A. Schmid, et al. Leukemic challenge unmasks a requirement for PI3K{delta} in NK cell-mediated tumor surveillance Blood, December 1, 2008; 112(12): 4655 - 4664. [Abstract] [Full Text] [PDF] A. W. MacFarlane IV, T. Yamazaki, M. Fang, L. J. Sigal, T. Kurosaki, and K. S. Campbell Enhanced NK-cell development and function in BCAP-deficient mice Blood, July 1, 2008; 112(1): 131 - 140. [Abstract] [Full Text] [PDF] S. Luangdilok, C. Box, L. Patterson, W. Court, K. Harrington, L. Pitkin, P. Rhys-Evans, P. O-charoenrat, and S. Eccles Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck Cancer Res., August 15, 2007; 67(16): 7907 - 7916. [Abstract] [Full Text] [PDF] I. L. Tourkova, G. V. Shurin, S. Wei, and M. R. Shurin Small Rho GTPases Mediate Tumor-Induced Inhibition of Endocytic Activity of Dendritic Cells J. Immunol., June 15, 2007; 178(12): 7787 - 7793. [Abstract] [Full Text] [PDF] L. S. Chaturvedi, H. M. Marsh, X. Shang, Y. Zheng, and M. D. Basson Repetitive Deformation Activates Focal Adhesion Kinase and ERK Mitogenic Signals in Human Caco-2 Intestinal Epithelial Cells through Src and Rac1 J. Biol. Chem., January 5, 2007; 282(1): 14 - 28. [Abstract] [Full Text] [PDF] U. A. Desai, J. Pallos, A. A. K. Ma, B. R. Stockwell, L. M. Thompson, J. L. Marsh, and M. I. Diamond Biologically active molecules that reduce polyglutamine aggregation and toxicity Hum. Mol. Genet., July 1, 2006; 15(13): 2114 - 2124. [Abstract] [Full Text] [PDF] A. Jewett, N. A. Cacalano, C. Head, and A. Teruel Coengagement of CD16 and CD94 receptors mediates secretion of chemokines and induces apoptotic death of naive natural killer cells. Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 1994 - 2003. [Abstract] [Full Text] [PDF] M. A. Belmonte, M. F. Santos, A. H. Kihara, C. Y. I. Yan, and D. E. Hamassaki Light-Induced Photoreceptor Degeneration in the Mouse Involves Activation of the Small GTPase Rac1. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 1193 - 1200. [Abstract] [Full Text] [PDF] R. Ain, L. N Canham, and M. J Soares Dexamethasone-induced intrauterine growth restriction impacts the placental prolactin family, insulin-like growth factor-II and the Akt signaling pathway J. Endocrinol., May 1, 2005; 185(2): 253 - 263. [Abstract] [Full Text] [PDF] K. Kawauchi, K. Ihjima, and O. Yamada IL-2 Increases Human Telomerase Reverse Transcriptase Activity Transcriptionally and Posttranslationally through Phosphatidylinositol 3'-Kinase/Akt, Heat Shock Protein 90, and Mammalian Target of Rapamycin in Transformed NK Cells J. Immunol., May 1, 2005; 174(9): 5261 - 5269. [Abstract] [Full Text] [PDF] M. D. Kaytor, C. E. Byam, S. K. Tousey, S. D. Stevens, H. Y. Zoghbi, and H. T. Orr A cell-based screen for modulators of ataxin-1 phosphorylation Hum. Mol. Genet., April 15, 2005; 14(8): 1095 - 1105. [Abstract] [Full Text] [PDF] N. W.C.J. van de Donk, H. M. Lokhorst, E. H.J. Nijhuis, M. M.J. Kamphuis, and A. C. Bloem Geranylgeranylated Proteins are Involved in the Regulation of Myeloma Cell Growth Clin. Cancer Res., January 15, 2005; 11(2): 429 - 439. [Abstract] [Full Text] [PDF] K. D. Moon, C. B. Post, D. L. Durden, Q. Zhou, P. De, M. L. Harrison, and R. L. Geahlen Molecular Basis for a Direct Interaction between the Syk Protein-tyrosine Kinase and Phosphoinositide 3-Kinase J. Biol. Chem., January 14, 2005; 280(2): 1543 - 1551. [Abstract] [Full Text] [PDF] M. Moroni, V. Soldatenkov, L. Zhang, Y. Zhang, G. Stoica, E. Gehan, B. Rashidi, B. Singh, M. Ozdemirli, and S. C. Mueller Progressive Loss of Syk and Abnormal Proliferation in Breast Cancer Cells Cancer Res., October 15, 2004; 64(20): 7346 - 7354. [Abstract] [Full Text] [PDF] B. Zhang, Y. Zhang, and E. Shacter Rac1 Inhibits Apoptosis in Human Lymphoma Cells by Stimulating Bad Phosphorylation on Ser-75 Mol. Cell. Biol., July 15, 2004; 24(14): 6205 - 6214. [Abstract] [Full Text] [PDF] F. Cerimele, L. F. Brown, F. Bravo, G. M. Ihler, P. Kouadio, and J. L Arbiser Infectious Angiogenesis: Bartonella bacilliformis Infection Results in Endothelial Production of Angiopoetin-2 and Epidermal Production of Vascular Endothelial Growth Factor Am. J. Pathol., October 1, 2003; 163(4): 1321 - 1327. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020