Tyrosine phosphorylation of both STAT5A and STAT5B is necessary for maximal IL-2 signaling and T cell proliferation.

Autor: Lin JX; Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA. linjx@nhlbi.nih.gov., Ge M; Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA.; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, PR China., Liu CY; Transgenic Mouse Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-8018, USA., Holewinski R; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, USA., Andresson T; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, USA., Yu ZX; Pathology Core, National Heart Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Gebregiorgis T; Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA., Spolski R; Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA., Li P; Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA.; Amgen, Inc., 2301 Research Blvd., Rockville, MD, 20850, USA., Leonard WJ; Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA. leonardw@nhlbi.nih.gov.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 27; Vol. 15 (1), pp. 7372. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1038/s41467-024-50925-6
Abstrakt: Cytokine-mediated STAT5 protein activation is vital for lymphocyte development and function. In vitro tyrosine phosphorylation of a C-terminal tyrosine is critical for activation of STAT5A and STAT5B; however, the importance of STAT5 tyrosine phosphorylation in vivo has not been assessed. Here we generate Stat5a and Stat5b tyrosine-to-phenylalanine mutant knockin mice and find they have greatly reduced CD8 + T-cell numbers and profoundly diminished IL-2-induced proliferation of these cells, and this correlates with reduced induction of Myc, pRB, a range of cyclins and CDKs, and a partial G1→S phase-transition block. These mutant CD8 + T cells also exhibit decreased IL-2-mediated activation of pERK and pAKT, which we attribute in part to diminished expression of IL-2Rβ and IL-2Rγ. Our findings thus demonstrate that tyrosine phosphorylation of both STAT5A and STAT5B is essential for maximal IL-2 signaling. Moreover, our transcriptomic and proteomic analyses elucidate the molecular basis of the IL-2-induced proliferation of CD8 + T cells.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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