PlumX Metrics
Embed PlumX Metrics

Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function

Immunity, ISSN: 1074-7613, Vol: 36, Issue: 4, Page: 586-599
2012
  • 152
    Citations
  • 0
    Usage
  • 202
    Captures
  • 1
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Most Recent News

An engineered IL-2 partial agonist promotes CD8+ T cell stemness

Nature, Published online: 15 September 2021; doi:10.1038/s41586-021-03861-0 H9T, an engineered IL-2 partial agonist, promotes the expansion of T cells while maintaining a stem-cell-like state, leading to improved efficacy of adoptive cell therapy in mouse models of melanoma and acute lymphoblastic leukaemia.

Article Description

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.

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know