DOI: 10.1073/pnas.94.8.3627. Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase

Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase

10.1073/pnas.94.8.3627

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The interleukin-2 (IL-2) receptor (IL-2R) is composed of three subunits. Of these, IL-2Rα is required for high-affinity IL-2 binding, while IL-2Rβ and IL-2Rγ c are required for the transduction of IL-2-generated signals. Signals transduced via the S region of the IL-2Rβ (amino acids 267–322) in BAF/3 cells activate the phosphatidylinositol 3-kinase (PI3-kinase) and induce the expression of Bcl-2 and c-myc. Through the induction of Bcl-2, IL-2 inhibits apoptosis and through the combination of Bcl-2 and c-myc it stimulates progression through the cell cycle. Here we show that the protein kinase encoded by the Akt proto-oncogene is activated by IL-2. Akt activation by IL-2 depends on PI3-kinase signals transduced via the S region of the IL-2Rβ and is linked to the translocation of Akt to the cell membrane. Expression of catalytically active Akt mutants in BAF/3 cells expressing IL-2Rβ[A0]ΔS promotes the expression of Bcl-2 and c-myc, inhibits apoptosis induced by IL-3 deprivation or staurosporine, and stimulates cell cycle progression. The same mutants also stimulate cell cycle progression in 2780a, an IL-2-dependent T cell line that undergoes G 1 arrest rather than apoptosis after IL-2 deprivation. The activation of Akt by IL-2 via the PI3-kinase and the rescue of the PI3-kinase-mediated antiapoptotic and proliferative IL-2 signals by catalytically active Akt indicate that these signals are transduced by Akt.

Bibliography

Ahmed, N. N., Grimes, H. L., Bellacosa, A., Chan, T. O., & Tsichlis, P. N. (1997). Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proceedings of the National Academy of Sciences, 94(8), 3627â3632.

Authors 5

Naheed N. Ahmed (first)
H. Leighton Grimes (additional)
Alfonso Bellacosa (additional)
Tung O. Chan (additional)
Philip N. Tsichlis (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 2:14 p.m.)
Indexed	2 months ago (June 27, 2025, 9:44 a.m.)
Issued	28 years, 4 months ago (April 15, 1997)
Published	28 years, 4 months ago (April 15, 1997)
Published Online	28 years, 4 months ago (April 15, 1997)
Published Print	28 years, 4 months ago (April 15, 1997)

Funders 0

None

BibTeX

@article{Ahmed_1997, title={Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.8.3627}, DOI={10.1073/pnas.94.8.3627}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Ahmed, Naheed N. and Grimes, H. Leighton and Bellacosa, Alfonso and Chan, Tung O. and Tsichlis, Philip N.}, year={1997}, month=apr, pages={3627–3632} }

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