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Series GSE247343 Query DataSets for GSE247343
Status Public on May 10, 2024
Title Tyrosine phosphorylation of both STAT5A and STAT5B is necessary for maximal IL-2 signaling and its mitogenic action
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary STAT5 proteins are vital for lymphocyte development and function. Cytokine activation of STAT5A and STAT5B involves the tyrosine phosphorylation of a C-terminal tyrosine in each protein; however, the importance of STAT5 tyrosine phosphorylation in vivo has not been assessed. Here we generated Stat5a and Stat5b tyrosine mutant knockin mice and found they had greatly reduced CD8+ T-cell numbers. Morever, these cells exhibited profoundly diminished IL-2-induced proliferation, correlating with reduced IL-2- mediated induction of Myc, pRB, a range of cyclins and CDKs, and a G1àS phase- transition block. The mutant CD8+ T 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-2Rb and IL-2Rg. Our findings demonstrate that tyrosine phosphorylation of both STAT5A and STAT5B is essential for maximal IL-2 signaling, and our transcriptomic and proteomic analyses elucidate the molecular basis for the mitogenic effects of IL-2 on CD8+ T cells.
Overall design ChIP-Seq and RNA-Seq analyses using freshly isolated mouse CD8+ T cells that were expanded with either no cytokine, or with IL-2 at various time points.
Contributor(s) Lin J, Ge M, Liu C, Holewinski R, Andresson T, Gebregiorgis T, Li P, Leonard WJ
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Submission date Nov 08, 2023
Last update date May 11, 2024
Contact name Peng Li
Organization name NIH
Department NHLBI
Street address 9000 Rockville Pike
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (57)
GSM7887458 RNASeq STAT5A.0h.WT rep1
GSM7887459 RNASeq STAT5A.0h.WT rep2
GSM7887460 RNASeq STAT5A.0h.WT rep3
BioProject PRJNA1037130

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Supplementary file Size Download File type/resource
GSE247343_RAW.tar 1.4 Gb (http)(custom) TAR (of BW, RPKM)
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Raw data are available in SRA

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