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EMBO J. 2018 Mar 1;37(5). pii: e96264. doi: 10.15252/embj.201696264. Epub 2018 Feb 15.

Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP-1.

Author information

1
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
2
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel mira.barda-saad@biu.ac.il.

Abstract

Natural killer (NK) cells are a powerful weapon against viral infections and tumor growth. Although the actin-myosin (actomyosin) cytoskeleton is crucial for a variety of cellular processes, the role of mechanotransduction, the conversion of actomyosin mechanical forces into signaling cascades, was never explored in NK cells. Here, we demonstrate that actomyosin retrograde flow (ARF) controls the immune response of primary human NK cells through a novel interaction between β-actin and the SH2-domain-containing protein tyrosine phosphatase-1 (SHP-1), converting its conformation state, and thereby regulating NK cell cytotoxicity. Our results identify ARF as a master regulator of the NK cell immune response. Since actin dynamics occur in multiple cellular processes, this mechanism might also regulate the activity of SHP-1 in additional cellular systems.

KEYWORDS:

NK cell signaling; SHP‐1; actin retrograde flow; cytotoxicity; natural killer cells

PMID:
29449322
PMCID:
PMC5830919
[Available on 2019-03-01]
DOI:
10.15252/embj.201696264
[Indexed for MEDLINE]

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