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

Helen Morrison, Larry S. Sherman, James Legg, Fatima Banine, Clare Isacke, Carrie A. Haipek, David H. Gutmann, Helmut Ponta, Peter Herrlich

    Research output: Contribution to journalArticle

    399 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)968-980
    Number of pages13
    JournalGenes and Development
    Volume15
    Issue number8
    DOIs
    StatePublished - Apr 15 2001

      Fingerprint

    Keywords

    • CD44
    • ERM
    • Ezrin
    • Hyaluronate
    • NF2
    • Schwann cells

    ASJC Scopus subject areas

    • Genetics
    • Developmental Biology

    Cite this