Receptor tyrosine kinase Tie-1 overexpression in endothelial cells upregulates adhesion molecules.
Tie-1 is an endothelial specific cell surface protein whose biology remains poorly understood. Using an overexpression system in vitro, we examined whether Tie-1 activity in endothelial cells in vitro would elicit a proinflammatory response. We found that when overexpressed in endothelial cells in vitro, Tie-1 is tyrosine-phosphorylated. We also showed that Tie-1 upregulates VCAM-1, E-selectin, and ICAM-1, partly through a p38-dependent mechanism. Interestingly, upregulation of VCAM-1 and E-selectin by Tie-1 is significantly higher in human aortic endothelial cells than in human umbilical vein endothelial cells. Additionally, attachment of cells of monocytic lineage to endothelial cells is also enhanced by Tie-1 expression. Collectively, our data show that Tie-1 has a proinflammatory property and may play a role in the endothelial inflammatory diseases such as atherosclerosis.
Chan
Barden
B
Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RW 563, Boston, MA 02215, USA.
Yuan
Hai-Tao
HT
Ananth Karumanchi
S
S
Sukhatme
Vikas P
VP
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000502:physiology; D010766:Phosphorylation; D042810:Receptor, TIE-1 / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D042810:Receptor, TIE-1; D048051:p38 Mitogen-Activated Protein Kinases