title: Acetylation Modulates IL-2 Receptor Signaling in T Cells.
abstract: Ligand binding to the cognate cytokine receptors activates intracellular signaling by recruiting protein tyrosine kinases and other protein modification enzymes. However, the roles of protein modifications other than phosphorylation remain unclear. In this study, we examine a novel regulatory mechanism of Stat5, based on its acetylation. As for phosphorylation, IL-2 induces the acetylation of signaling molecules, including Stat5, in the murine T cell line CTLL-2. Stat5 is acetylated in the cytoplasm by CREB-binding protein (CBP). Acetylated Lys696and Lys700on Stat5 are critical indicators for limited proteolysis, which leads to the generation of a truncated form of Stat5. In turn, the truncated form of Stat5 prevents transcription of the full-length form of Stat5. We also demonstrate that CBP physically associates with the IL-2 receptor β-chain. CBP, found in the nucleus in resting CTLL-2 cells, relocates to the cytoplasm after IL-2 stimulation in an MEK/ERK pathway-dependent manner. Thus, IL-2-mediated acetylation plays an important role in the modulation of cytokine signaling and T cell fate.
authors: Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan; and kuwabara@med.toho-u.ac.jp.
authors: Taku
authors: 0000-0001-5985-8245
authors: T
authors: Kuwabara
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors: Hirotake
authors: H
authors: Kasai
authors: Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan; and.
authors: Motonari
authors: 0000-0002-1565-8804
authors: M
authors: Kondo
mesh_terms: D000107:Acetylation; D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D059748:Proteolysis; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: C508022:Il2rb protein, mouse; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D050799:STAT5 Transcription Factor; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse