DLGH1 is a negative regulator of T-lymphocyte proliferation

Stephenson, Linda M.; Sammut, B�n�dicte; Graham, Daniel B.; Chan-Wang, Joaquim; Brim, Karry L.; Huett, Alan S.; Miletic, Ana V.; Kloeppel, Tracie; Landry, Aimee; Xavier, Ramnik; Swat, Wojciech

Abstract

Discs large homolog 1 (DLGH1), a founding member of the membrane-associated guanylate kinase family of proteins containing Postsynaptic Density-95/Discs large/Zona Occludens-1 domains, is an ortholog of the Drosophila tumor suppressor gene Discs large. In the mammalian embryo, DLGH1 is essential for normal urogenital morphogenesis and the development of skeletal and epithelial structures. Recent reports also indicate that DLGH1 may be a critical mediator of signals triggered by the antigen receptor complex in T lymphocytes by functioning as a scaffold coordinating the activities of T-cell receptor (TCR) signaling proteins at the immune synapse. However, it remains unclear if DLGH1 functions to enhance or attenuate signals emanating from the TCR. Here, we used Dlgh1 gene-targeted mice to determine the requirement for DLGH1 in T-cell development and activation. Strikingly, while all major subsets of T cells appear to undergo normal thymic development in the absence of DLGH1, peripheral lymph node Dlgh1-/- T cells show a hyperproliferative response to TCR-induced stimulation. These data indicate that, consistent with the known function of Discs large proteins as tumor suppressors and attenuators of cell division, in T lymphocytes, DLGH1 functions as a negative regulator of TCR-induced proliferative responses. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Citation

Stephenson, L. M., Sammut, B., Graham, D. B., Chan-Wang, J., Brim, K. L., Huett, A. S., Miletic, A. V., Kloeppel, T., Landry, A., Xavier, R., & Swat, W. (2007). DLGH1 is a negative regulator of T-lymphocyte proliferation. Molecular and Cellular Biology, 27(21), 7574-7581. https://doi.org/10.1128/MCB.00439-07

• Journal Article Type: Article
• Acceptance Date: Aug 10, 2007
• Online Publication Date: Aug 27, 2007
• Publication Date: Nov 1, 2007
• Deposit Date: Aug 15, 2022
• Journal: Molecular and Cellular Biology
• Print ISSN: 0270-7306
• Electronic ISSN: 1098-5549
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 21
• Pages: 7574-7581
• DOI: https://doi.org/10.1128/MCB.00439-07
• Public URL: https://nottingham-repository.worktribe.com/output/3181874
• Publisher URL: https://journals.asm.org/doi/10.1128/MCB.00439-07