Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion

Nat Immunol. 2006 Sep;7(9):919-28. doi: 10.1038/ni1374. Epub 2006 Aug 6.


RAPL, a protein that binds the small GTPase Rap1, is required for efficient immune cell trafficking. Here we have identified the kinase Mst1 as a critical effector of RAPL. RAPL regulated the localization and kinase activity of Mst1. 'Knockdown' of the gene encoding Mst1 demonstrated its requirement for the induction of both a polarized morphology and integrin LFA-1 clustering and adhesion triggered by chemokines and T cell receptor ligation. RAPL and Mst1 localized to vesicular compartments and dynamically translocated with LFA-1 to the leading edge upon Rap1 activation, suggesting a regulatory function for the RAPL-Mst1 complex in intracellular transport of LFA-1. Our study demonstrates a previously unknown function for Mst1 of relaying the Rap1-RAPL signal to induce cell polarity and adhesion of lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion* / genetics
  • Cell Polarity* / genetics
  • Hepatocyte Growth Factor / agonists
  • Hepatocyte Growth Factor / analysis
  • Hepatocyte Growth Factor / metabolism*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Lymphocytes / chemistry
  • Lymphocytes / metabolism*
  • Lymphocytes / ultrastructure
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Protein Transport
  • Proto-Oncogene Proteins / agonists
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / metabolism*
  • Transport Vesicles / chemistry
  • Transport Vesicles / metabolism
  • Up-Regulation
  • rap1 GTP-Binding Proteins / agonists
  • rap1 GTP-Binding Proteins / analysis
  • rap1 GTP-Binding Proteins / genetics
  • rap1 GTP-Binding Proteins / metabolism*


  • Lymphocyte Function-Associated Antigen-1
  • Proto-Oncogene Proteins
  • RAPL protein, mouse
  • macrophage stimulating protein
  • Hepatocyte Growth Factor
  • rap1 GTP-Binding Proteins