Noncanonical Hippo Signalling in the Regulation of Leukocyte Function

Trends Immunol. 2018 Aug;39(8):656-669. doi: 10.1016/j.it.2018.05.003. Epub 2018 Jun 26.

Abstract

The mammalian sterile 20-like (MST) kinases are central constituents of the evolutionary ancient canonical Hippo pathway regulating cell proliferation and survival. However, perhaps surprisingly, MST1 deficiency in human patients leads to a severe combined immunodeficiency syndrome with features of autoimmune disease. In line with this, Mst1-deficient mice exhibit severe defects in lymphocyte and neutrophil functions as well as disturbed intracellular vesicle transport. These findings spurred research on the noncanonical functions of MST1 in leukocytes. Here, we summarise the latest findings on this topic and discuss MST1 as a critical regulator of various leukocyte functions.

Keywords: Hippo pathway; MST1; MST2; leukocyte; vesicle transport.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics*
  • Biological Evolution
  • Hippo Signaling Pathway
  • Humans
  • Leukocytes / metabolism*
  • MAP Kinase Kinase Kinases / genetics*
  • MAP Kinase Kinase Kinases / metabolism
  • Mice
  • Protein Serine-Threonine Kinases / metabolism*
  • Severe Combined Immunodeficiency / genetics*
  • Signal Transduction

Substances

  • Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases
  • MAP3K10 protein, human