Journal
GENES & DEVELOPMENT
Volume 15, Issue 8, Pages 968-980Publisher
COLD SPRING HARBOR LAB PRESS
DOI: 10.1101/gad.189601
Keywords
NF2; CD44; ezrin; hyaluronate; ERM; Schwann cells
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Funding
- NINDS NIH HHS [NS 39550, NS 35848, R01 NS035848] Funding Source: Medline
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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 lear 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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