101. Evidence for Heterotypic Interaction between the Receptor Tyrosine Kinases TIE-1 and TIE-2
- Author
-
David P. Hughes, Cheryl L. Forder, Marie B. Marron, Nicholas P.J. Brindle, and Edge Michael Derek
- Subjects
Umbilical Veins ,Saccharomyces cerevisiae Proteins ,Receptors, Cell Surface ,Tropomyosin receptor kinase B ,Ligands ,Transfection ,SH2 domain ,Biochemistry ,Tropomyosin receptor kinase C ,Receptor tyrosine kinase ,Receptors, TIE ,Humans ,Endothelium ,Phosphorylation ,Receptor, trkA ,Phosphotyrosine ,Cation Transport Proteins ,Molecular Biology ,Orphan receptor ,G protein-coupled receptor kinase ,biology ,Cell Membrane ,Phosphotransferases ,Receptor Protein-Tyrosine Kinases ,Receptor, TIE-1 ,Cell Biology ,Precipitin Tests ,Receptor, TIE-2 ,Protein Structure, Tertiary ,Cell biology ,ROR1 ,biology.protein ,Endothelium, Vascular ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
The orphan receptor tyrosine kinase Tie-1 is expressed in endothelial cells and is essential for vascular development. Nothing is known about the signaling pathways utilized by this receptor. In this study we have used chimeric receptors composed of the TrkA ectodomain fused to the transmembrane and intracellular domains of Tie-1, or the related receptor Tie-2, to examine Tie-1 signaling capacity. In contrast to TrkA/Tie-2, the Tie-1 chimera was unable to phosphorylate cellular proteins or undergo autophosphorylation. Consistent with this Tie-1 exhibited negligible kinase activity. Co-immunoprecipitation analysis revealed Tie-1 was present in endothelial cells bound to Tie-2. Full-length Tie-1 and truncated receptor, formed by regulated endoproteolytic cleavage, were found to complex with Tie-2. Association was mediated by the intracellular domains of the receptors and did not require Tie-1 to be membrane-localized. Tie-1 bound to Tie-2 was not tyrosine-phosphorylated under basal conditions or following Tie-2 stimulation. This study provides the first evidence for the existence of a pre-formed complex of Tie-1 and Tie-2 in endothelial cells. The data suggest Tie-1 does not signal via ligand-induced kinase activation involving homo-oligomerization. The physical association between Tie-1 and Tie-2 is consistent with Tie-1 having a role in modulating Tie-2 signaling.
- Published
- 2000
- Full Text
- View/download PDF