PECAM-1 promotes beta-catenin accumulation and stimulates endothelial cell proliferation.
Platelet endothelial cell adhesion molecule-1 (PECAM-1) binds tyrosine phosphorylated beta-catenin and modulates beta-catenin localization [J. Immunol. 158 (7) (1997) 3408; J. Cell Sci. 112 (Pt 18) (1999) 3005]. To elucidate functional consequences of this interaction, we studied endothelial cells from PECAM-1 knockout animals and compared them to PECAM-1 expressing endothelial cells [Mol. Biol. Cell 11 (9) (2000) 3109]. We noted an increase in the expression of beta-catenin protein in PECAM-1 expressing endothelial cells. Further, by immunofluorescence, beta-catenin localized to the cell membrane as well as to the nucleus in PECAM-1 positive endothelial cells, whereas cells not expressing PECAM-1 stained for beta-catenin only at the membrane. Additionally, we demonstrate that PECAM-1 lacking the majority of the cytoplasmic domain promotes significantly less accumulation of transcriptionally active beta-catenin than full-length PECAM-1. Finally, we note an increased proliferative rate in the PECAM-1 reconstituted cells compared to the endothelial cells lacking PECAM-1. Taken together, our data suggest that PECAM-1, an adhesion molecule, affects cell proliferation via accumulation of transcriptionally active beta-catenin.
Biswas
Purba
P
Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Canosa
Sandra
S
Schoenfeld
Jonathan
J
Schoenfeld
David
D
Tucker
Adeline
A
Madri
Joseph A
JA
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002455:Cell Division; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004727:Endothelium / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism* / Q000502:physiology*; D011233:Precipitin Tests; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D051176:beta Catenin
D000199:Actins; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015534:Trans-Activators; D051176:beta Catenin