DOI: 10.1084/jem.192.1.99. Negative Regulation of T Cell Proliferation and Interleukin 2 Production by the Serine Threonine Kinase Gsk-3

Negative Regulation of T Cell Proliferation and Interleukin 2 Production by the Serine Threonine Kinase Gsk-3

10.1084/jem.192.1.99

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Glycogen synthase kinase (GSK)-3 is a protein serine/threonine kinase that regulates differentiation and cell fate in a variety of organisms. This study examined the role of GSK-3 in antigen-specific T cell responses. Using resting T cells from P14 T cell receptor (TCR)-transgenic mice (specific for the lymphocytic choriomeningitis virus and H-2Db), we demonstrated that GSK-3β was inactivated by serine phosphorylation after viral peptide–specific stimulation in vitro. To further investigate the role of GSK-3, we have generated a retroviral vector that expresses a constitutively active form of GSK-3β that has an alanine substitution at the regulatory amino acid, serine 9 (GSK-3βA9). Retroviral transduction of P14 TCR–transgenic bone marrow stem cells, followed by reconstitution, led to the expression of GSK-3βA9 in bone marrow chimeric mice. T cells from chimeric mice demonstrate a reduction in proliferation and interleukin (IL)-2 production. In contrast, in vitro assays done in the presence of the GSK-3 inhibitor lithium led to dramatically prolonged T cell proliferation and increased IL-2 production. Furthermore, in the presence of lithium, we show that nuclear factor of activated T cells (NF-AT)c remains in the nucleus after antigen-specific stimulation of T cells. Together, these data demonstrate that GSK-3 negatively regulates the duration of T cell responses.

Authors 7

Toshiaki Ohteki (first)
Michael Parsons (additional)
Arsen Zakarian (additional)
Russell G. Jones (additional)
Linh T. Nguyen (additional)
James R. Woodgett (additional)
Pamela S. Ohashi (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 6:35 a.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 3:07 p.m.)
Issued	25 years, 1 month ago (July 3, 2000)
Published	25 years, 1 month ago (July 3, 2000)
Published Online	25 years, 1 month ago (July 3, 2000)
Published Print	25 years, 1 month ago (July 3, 2000)

Funders 0

None

BibTeX

@article{Ohteki_2000, title={Negative Regulation of T Cell Proliferation and Interleukin 2 Production by the Serine Threonine Kinase Gsk-3}, volume={192}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.192.1.99}, DOI={10.1084/jem.192.1.99}, number={1}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Ohteki, Toshiaki and Parsons, Michael and Zakarian, Arsen and Jones, Russell G. and Nguyen, Linh T. and Woodgett, James R. and Ohashi, Pamela S.}, year={2000}, month=jul, pages={99–104} }

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