Characterization and regulation of the receptor tyrosine kinase Tie-1 in platelets
| Autor: | Helen Box, Nicholas P.J. Brindle, Peter R.F. Bell, Alison H. Goodall, Achilleas C. Tsiamis, Paul D. Hayes |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Blood Platelets Umbilical Veins Physiology Blotting Western Neovascularization Physiologic Receptors Cell Surface Tropomyosin receptor kinase B Biology Tropomyosin receptor kinase C Receptor tyrosine kinase Receptors TIE Humans Protease-activated receptor Protease Inhibitors Platelet activation Cells Cultured Thrombin Receptor Protein-Tyrosine Kinases Receptor TIE-1 Platelet Activation Receptor TIE-2 Cell biology Protein Structure Tertiary Adenosine Diphosphate Molecular Weight Biochemistry Organ Specificity ROR1 biology.protein Tetradecanoylphorbol Acetate Endothelium Vascular Signal transduction Cardiology and Cardiovascular Medicine Tyrosine kinase |
| Zdroj: | Journal of vascular research. 37(6) |
| ISSN: | 1018-1172 |
| Popis: | The receptor tyrosine kinase Tie-1 is expressed predominantly on endothelial cells where it has an essential role in blood vessel formation. Targeted disruption of the Tie-1 gene results in a lethal phenotype with severe disruption to the normal integrity of the vasculature. In an examination of Tie-1 in vivo, we observed a significant pool of the receptor present in the circulation associated with the platelet fraction. Western blotting reveals the platelet form of Tie-1 to be a protein of approximately 110 kDa, this contrasts with the 135/125-kDa doublet found in endothelial cells. Platelet activation results in increased surface expression of Tie-1. The closely related receptor tyrosine kinase Tie-2/Tek is not present in platelets. Endothelial Tie-1 undergoes metalloprotease-mediated ectodomain cleavage in response to phorbol ester and other agonists. Tie-1 cleavage leads to release of the extracellular domain and generation of a cell-associated intracellular domain with signalling capacity. The potential for cleavage was investigated in platelets. In contrast to endothelial Tie-1, phorbol ester does not stimulate truncation of the platelet receptor, suggesting these cells lack one or more components of the regulated metalloprotease system controlling Tie-1. These data demonstrate the Tie-1 receptor tyrosine kinase is present on platelets and its surface expression is regulated. Furthermore, platelet Tie-1 differs significantly from the endothelial receptor. Platelet Tie-1 has the potential to modulate endothelial function by competing for any Tie ligands and may have signalling roles important in controlling aspects of platelet behaviour. |
| Databáze: | OpenAIRE |
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