Characterization and Regulation of the Receptor Tyrosine Kinase Tie-1 in Platelets

• Published in: Journal of vascular research Vol. 37; no. 6; pp. 437 - 442
• Main Authors: Tsiamis, Achilleas C., Hayes, Paul, Box, Helen, Goodall, Alison H., Bell, Peter R.F., Brindle, Nicholas P.J.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Basel, Switzerland Karger 01.11.2000
• Subjects: Adenosine Diphosphate - pharmacology; Adult; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - enzymology; Blood vessels and receptors; Blotting, Western; Cells, Cultured; Endothelium, Vascular - enzymology; Fundamental and applied biological sciences. Psychology; Humans; Internet Discussion Forum; Molecular and cellular biology; Molecular Weight; Neovascularization, Physiologic; Organ Specificity; Platelet; Platelet Activation; Protease Inhibitors - pharmacology; Protein Structure, Tertiary; Receptor Protein-Tyrosine Kinases - blood; Receptor Protein-Tyrosine Kinases - chemistry; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - physiology; Receptor, TIE-1; Receptor, TIE-2; Receptors, Cell Surface - agonists; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - genetics; Receptors, Cell Surface - physiology; Receptors, TIE; Tetradecanoylphorbol Acetate - pharmacology; Thrombin - pharmacology; Umbilical Veins; Vertebrates: cardiovascular system; Angiogenesis; Tie; Tyrosine kinase; Platelet; Endothelial cell; Signalling; Human; Enzyme; Transferases; Gene expression; Signal transduction; Blood cell; Regulation(control); Blood vessel; Circulatory system; Protein-tyrosine kinase; Umbilical vein; Biological receptor
• ISSN: 1018-1172; 1423-0135
• DOI: 10.1159/000054075

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.