A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation.
Journal
Genes and immunity
ISSN: 1476-5470
Titre abrégé: Genes Immun
Pays: England
ID NLM: 100953417
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
18
03
2019
accepted:
14
08
2019
revised:
08
08
2019
pubmed:
9
10
2019
medline:
7
1
2021
entrez:
9
10
2019
Statut:
ppublish
Résumé
The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induced W484G mutation in the Stat5a gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from Stat5a mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of Stat5a mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that Stat5a mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. Overall, our results demonstrate that the W484G mutation in the linker domain of STAT5A is sufficient to compromise STAT5A function in NK-cell homeostasis, responsiveness, and tumoricidal function.
Identifiants
pubmed: 31591503
doi: 10.1038/s41435-019-0088-6
pii: 10.1038/s41435-019-0088-6
doi:
Substances chimiques
DNA-Binding Proteins
0
STAT5 Transcription Factor
0
Stat5a protein, mouse
0
Trans-Activators
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
136-141Références
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