Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_1D70F1981844
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells.
Journal
Nature communications
Author(s)
Niogret C., Miah SMS, Rota G., Fonta N.P., Wang H., Held W., Birchmeier W., Sexl V., Yang W., Vivier E., Ho P.C., Brossay L., Guarda G.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
29/03/2019
Peer-reviewed
Oui
Volume
10
Number
1
Pages
1444
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
The phosphatase Shp-2 was implicated in NK cell development and functions due to its interaction with NK inhibitory receptors, but its exact role in NK cells is still unclear. Here we show, using mice conditionally deficient for Shp-2 in the NK lineage, that NK cell development and responsiveness are largely unaffected. Instead, we find that Shp-2 serves mainly to enforce NK cell responses to activation by IL-15 and IL-2. Shp-2-deficient NK cells have reduced proliferation and survival when treated with high dose IL-15 or IL-2. Mechanistically, Shp-2 deficiency hampers acute IL-15 stimulation-induced raise in glycolytic and respiration rates, and causes a dramatic defect in ERK activation. Moreover, inhibition of the ERK and mTOR cascades largely phenocopies the defect observed in the absence of Shp-2. Together, our data reveal a critical function of Shp-2 as a molecular nexus bridging acute IL-15 signaling with downstream metabolic burst and NK cell expansion.
Keywords
Animals, Antigens, Ly/metabolism, Cell Count, Cell Proliferation/drug effects, Cell Size/drug effects, Enzyme Activation/drug effects, Extracellular Signal-Regulated MAP Kinases/metabolism, Integrases/metabolism, Interleukin-15/pharmacology, Killer Cells, Natural/drug effects, Killer Cells, Natural/metabolism, Mice, Inbred C57BL, Mice, Knockout, Muromegalovirus/physiology, Natural Cytotoxicity Triggering Receptor 1/metabolism, Protein Tyrosine Phosphatase, Non-Receptor Type 11/deficiency, Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism, Receptors, Interleukin-15/metabolism, TOR Serine-Threonine Kinases/metabolism
Pubmed
Web of science
Create date
03/04/2019 15:22
Last modification date
20/08/2019 13:53
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