The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44.
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.
Morrison
H
H
Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, and University of Karlsruhe, Institute of Genetics, 76021 Karlsruhe, Germany.
Sherman
L S
LS
Legg
J
J
Banine
F
F
Isacke
C
C
Haipek
C A
CA
Gutmann
D H
DH
Ponta
H
H
Herrlich
P
P
D016475:3T3 Cells; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D003598:Cytoskeletal Proteins; D004285:Dogs; D005109:Extracellular Matrix; D016147:Genes, Tumor Suppressor; D005982:Glutathione Transferase / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000494:pharmacology; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D008954:Models, Biological; D025581:Neurofibromin 2; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D000099149:Ezrin
D000276:Adjuvants, Immunologic; D003598:Cytoskeletal Proteins; D005982:Glutathione Transferase; D006025:Glycosaminoglycans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D008024:Ligands; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025581:Neurofibromin 2; D010750:Phosphoproteins; D000099149:Ezrin; C071058:moesin