MassIVE MSV000093724

Partial Public

Essential role of STAT5 tyrosine phosphorylation in vivo

Description

STAT5 proteins are vital for lymphocyte development and function. Tyrosine phosphorylation of a C-terminal tyrosine is the key event in cytokine activation of STAT5A and STAT5B. However, the role of STAT5 tyrosine phosphorylation has not been assessed in vivo. Here we generated Stat5a and Stat5b tyrosine mutant knock-in (KI) mice and found that these animals had greatly reduced CD8+ T cell numbers. These cells exhibited profoundly diminished proliferation in response to IL-2, correlating with greatly reduced IL-2-induced pRB and a block in the G1-->S phase transition. The mutant cells also exhibited decreased IL-2-mediated activation of pERK and pAKT, which can in part be attributed to diminished IL-2-induced expression of IL-2R-beta and IL-2R-gamma. Our findings highlight that the tyrosine phosphorylation of both STAT5A and STAT5B is essential for maximal IL-2 signaling and elucidate the molecular basis for achieving an optimal mitogenic effect of IL-2 on CD8+ T cells. [doi:10.25345/C5833N851] [dataset license: CC0 1.0 Universal (CC0 1.0)] [doi:10.25345/C5XK85185] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Stat5, cytokine, IL-2, T cell, NK cell, tyrosine phosphorylation

Contact

Principal Investigators:
(in alphabetical order)
Warren Leonard, National Institute of Health, National Heart, Lung , and Blood Institute, United States
Submitting User: ronholes7059
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