The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44
- Helen Morrison1,
- Larry S. Sherman2,
- James Legg3,
- Fatima Banine2,
- Clare Isacke3,
- Carrie A. Haipek4,
- David H. Gutmann4,
- Helmut Ponta1, and
- Peter Herrlich1,5
- 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.
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Footnotes
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↵5 Corresponding author.
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E-MAIL peter.herrlich{at}itg.fzk.de; FAX 49-7247-823354.
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Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.189601.
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- Received August 8, 2000.
- Accepted February 16, 2001.
- Cold Spring Harbor Laboratory Press