Other
13 Authors
- Rochman Y,
- Kelsall BL,
- Liu C,
- Li P,
- Liu D,
- He J,
- Jin HT,
- Wang L,
- Lin JX,
- Ata Ur Rasheed M,
- Cui K,
- Ahmed R,
- Leonard WJ
| First Author | Lin JX | Year | 2012 |
| Journal | Immunity | Volume | 36 |
| Issue | 4 | Pages | 586-99 |
| PubMed ID | 22520852 | Mgi Jnum | J:187325 |
| Mgi Id | MGI:5436197 | Doi | 10.1016/j.immuni.2012.02.017 |
| Citation | Lin JX, et al. (2012) Critical Role of STAT5 transcription factor tetramerization for cytokine responses and normal immune function. Immunity 36(4):586-99 |
| abstractText | Cytokine-activated STAT proteins dimerize and bind to high-affinity motifs, and N-terminal domain-mediated oligomerization of dimers allows tetramer formation and binding to low-affinity tandem motifs, but the functions of dimers versus tetramers are unknown. We generated Stat5a-Stat5b double knockin (DKI) N-domain mutant mice in which STAT5 proteins form dimers but not tetramers, identified cytokine-regulated genes whose expression required STAT5 tetramers, and defined dimer versus tetramer consensus motifs. Whereas Stat5-deficient mice exhibited perinatal lethality, DKI mice were viable; thus, STAT5 dimers were sufficient for survival. Nevertheless, STAT5 DKI mice had fewer CD4(+)CD25(+) T cells, NK cells, and CD8(+) T cells, with impaired cytokine-induced and homeostatic proliferation of CD8(+) T cells. Moreover, DKI CD8(+) T cell proliferation after viral infection was diminished and DKI Treg cells did not efficiently control colitis. Thus, tetramerization of STAT5 is critical for cytokine responses and normal immune function, establishing a critical role for STAT5 tetramerization in vivo. |
