The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Activation of PI3K Is Indispensable for Interleukin 7–mediated Viability, Proliferation, Glucose Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells
Open accessAbstract
Interleukin (IL)-7 is essential for normal T cell development. Previously, we have shown that IL-7 increases viability and proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells by up-regulating Bcl-2 and down-regulating the cyclin-dependent kinase inhibitor p27kip1. Here, we examined the signaling pathways via which IL-7 mediates these effects. We investigated mitogen-activated protein kinase (MEK)–extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)–Akt (protein kinase B) pathways, which have active roles in T cell expansion and have been implicated in tumorigenesis. IL-7 induced activation of the MEK–Erk pathway in T-ALL cells; however, inhibition of the MEK–Erk pathway by the use of the cell-permeable inhibitor PD98059, did not affect IL-7–mediated viability or cell cycle progression of leukemic cells. IL-7 induced PI3K-dependent phosphorylation of Akt and its downstream targets GSK-3, FOXO1, and FOXO3a. PI3K activation was mandatory for IL-7–mediated Bcl-2 up-regulation, p27kip1 down-regulation, Rb hyperphosphorylation, and consequent viability and cell cycle progression of T-ALL cells. PI3K signaling was also required for cell size increase, up-regulation of CD71, expression of the glucose transporter Glut1, uptake of glucose, and maintenance of mitochondrial integrity. Our results implicate PI3K as a major effector of IL-7–induced viability, metabolic activation, growth and proliferation of T-ALL cells, and suggest that PI3K and its downstream effectors may represent molecular targets for therapeutic intervention in T-ALL.
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Metabolic regulation of immune responses
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Metabolic switching and fuel choice during T‐cell differentiation and memory development
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Metadata
- Authors
- Barata, J. T., Silva, A., Brandao, J. G., Nadler, L. M., Cardoso, A. A., & Boussiotis, V. A.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2004-09-06
- Volume
- 200
- Issue
- 5
- Pages
- 659-669
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2149627687
- Cited by
- 284
- References
- 60
- FWCI
- 8.94
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Barata, J. T., Silva, A., Brandao, J. G., Nadler, L. M., Cardoso, A. A., & Boussiotis, V. A. (2004). Activation of PI3K Is Indispensable for Interleukin 7–mediated Viability, Proliferation, Glucose Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20040789
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