Characterization and regulation of the receptor tyrosine kinase Tie-1 in platelets.
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.
Tsiamis
A C
AC
Department of Surgery, University of Leicester, RKCSB, Leicester, UK.
Hayes
P
P
Box
H
H
Goodall
A H
AH
Bell
P R
PR
Brindle
N P
NP
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000201:enzymology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology; D006801:Humans; D008970:Molecular Weight; D018919:Neovascularization, Physiologic; D009928:Organ Specificity; D015539:Platelet Activation; D011480:Protease Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D011956:Receptors, Cell Surface / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D042764:Receptors, TIE; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins
D011480:Protease Inhibitors; D011956:Receptors, Cell Surface; D000244:Adenosine Diphosphate; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D042764:Receptors, TIE; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate