Overexpression of p101 activates PI3Kγ signaling in T cells and contributes to cell survival
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...
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Published in | Oncogene Vol. 26; no. 49; pp. 7049 - 7057 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Basingstoke
Nature Publishing
25.10.2007
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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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ISSN: | 0950-9232 1476-5594 |
DOI: | 10.1038/sj.onc.1210504 |