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

Omri Matalon, Aviad Ben-Shmuel, Jessica Kivelevitz, Batel Sabag, Sophia Fried, Noah Joseph, Elad Noy, Guy Biber, Mira Barda-Saad

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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.

Original languageEnglish
Article numbere96264
JournalEMBO Journal
Issue number5
StatePublished - 1 Mar 2018

Bibliographical note

Funding Information:
The authors thank Mr. Tevie Mehlman, from the Mass spectrometry unit, Weizmann institute of science, Dr. Yael Shinar, from the Sheba Medical Center, Israel, and Dr. Yarden Opatowsky, from the Faculty of Life Sciences, Bar-Ilan University, Israel, for their kind assistance. This research was funded by the Israel Science Foundation (ISF) grants no. 1503/08 and 747/13, grant no. 3-10151 from the Chief Scientist Office of the Ministry of Health, and a Taubenblatt Family Foundation Bio-Medicine excellence grant.

Publisher Copyright:
© 2018 The Authors


  • NK cell signaling
  • SHP-1
  • actin retrograde flow
  • cytotoxicity
  • natural killer cells


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