The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44

  1. Helen Morrison1,
  2. Larry S. Sherman2,
  3. James Legg3,
  4. Fatima Banine2,
  5. Clare Isacke3,
  6. Carrie A. Haipek4,
  7. David H. Gutmann4,
  8. Helmut Ponta1, and
  9. Peter Herrlich1,5
  1. 1Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, and University of Karlsruhe, Institute of Genetics, 76021 Karlsruhe, Germany; 2Department of Cell Biology, Neurobiology & Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA; 3Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK, 4Department of Neurology, Washington University Medical School, St. Louis, Missouri 63110, USA

Abstract

The neurofibromatosis-2 (NF2) gene encodes merlin, an ezrin-radixin-moesin-(ERM)-related protein that functions as a tumor suppressor. We found that merlin mediates contact inhibition of growth through signals from the extracellular matrix. At high cell density, merlin becomes hypo-phosphorylated and inhibits cell growth in response to hyaluronate (HA), a mucopolysaccharide that surrounds cells. Merlin's growth-inhibitory activity depends on specific interaction with the cytoplasmic tail of CD44, a transmembrane HA receptor. At low cell density, merlin is phosphorylated, growth permissive, and exists in a complex with ezrin, moesin, and CD44. These data indicate that merlin and CD44 form a molecular switch that specifies cell growth arrest or proliferation.

Keywords

Footnotes

  • 5 Corresponding author.

  • E-MAIL peter.herrlich{at}itg.fzk.de; FAX 49-7247-823354.

  • Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.189601.

    • Received August 8, 2000.
    • Accepted February 16, 2001.
| Table of Contents

Life Science Alliance