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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
3T3 Cells
-
Adjuvants, Immunologic / pharmacology
-
Animals
-
Blotting, Western
-
Cell Division
-
Cell Line
-
Cytoskeletal Proteins
-
Dogs
-
Extracellular Matrix
-
Genes, Tumor Suppressor
-
Glutathione Transferase / metabolism
-
Glycosaminoglycans / metabolism
-
Hyaluronan Receptors / metabolism*
-
Hyaluronic Acid / pharmacology
-
Ligands
-
Membrane Proteins / genetics*
-
Membrane Proteins / metabolism
-
Membrane Proteins / physiology
-
Mice
-
Microfilament Proteins / metabolism
-
Models, Biological
-
Neurofibromin 2
-
Phosphoproteins / metabolism
-
Phosphorylation
-
Rats
-
Signal Transduction
-
Time Factors
Substances
-
Adjuvants, Immunologic
-
Cytoskeletal Proteins
-
Glycosaminoglycans
-
Hyaluronan Receptors
-
Ligands
-
Membrane Proteins
-
Microfilament Proteins
-
Neurofibromin 2
-
Phosphoproteins
-
ezrin
-
moesin
-
Hyaluronic Acid
-
Glutathione Transferase