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Overexpression of p101 activates PI3Kγ signaling in T cells and contributes to cell survival

Oncogene volume 26, pages 7049–7057 (2007)Cite this article

Abstract

p101, the regulatory subunit of phosphatidylinositol-3-kinase-gamma (PI3Kγ), was recently reported as a common site of retroviral insertion in T-cell lymphomas induced in mice by MoFe2-MuLV, a unique recombinant gammaretrovirus. The common interruption of p101 by retroviral integration suggests that the locus encodes an oncogene whose altered expression is related to the induction of T-cell malignancy. To examine a possible role in the malignant process, p101 was overexpressed in human T-cell lines Molt-4 and Jurkat. Transient overexpression of p101 induced apoptosis in recipient cells; however, stable expression could be established in cells that expressed moderate levels of p101. Constitutive p101 overexpression in those cells conferred significant protection against ultraviolet-induced apoptosis. Protection against apoptotic induction was attributed to p101-mediated activation of the Akt pathway. Constitutive overexpression of p101 enhanced the activity of p110γ and further sensitized it to activation upon stimulation of G protein-coupled receptor. These findings are the first to implicate altered expression of p101 in malignancy, specifically in T-cell lymphoma. The findings further provide insight into the regulation of p110γ, indicating that the stoichiometry of p110γ and p101 are important in regulating PI3Kγ signaling.

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Acknowledgements

We acknowledge the valuable advice and assistance of Aline Scandurro, Kent Buchanan and Chandtip Chandhasin. This work was supported by PHS grant CA83823 from the National Cancer Institute, by a grant from the Ladies Leukemia League and by Support Funds of the Louisiana Cancer Research Consortium. Chassidy Johnson was supported in part by grants from the Cancer Association of Greater New Orleans and the American Association for Cancer Research Save the Science Fund.

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  1. Department of Microbiology and Immunology and Tulane Cancer Center, Tulane University Health Sciences Center, New Orleans, LA, USA

    C Johnson & L S Levy

  2. Department of Molecular Virology and Microbiology and Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX, USA

    S J Marriott

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Correspondence to L S Levy.

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Johnson, C., Marriott, S. & Levy, L. Overexpression of p101 activates PI3Kγ signaling in T cells and contributes to cell survival. Oncogene 26, 7049–7057 (2007). https://doi.org/10.1038/sj.onc.1210504

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