A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains.

Abstract

Endothelial cell surfaces play key roles in several important physiological and pathological processes such as blood clotting, angiogenic responses, and inflammation. Here we describe the cloning and characterization of tie, a novel type of human endothelial cell surface receptor tyrosine kinase. The extracellular domain of the predicted tie protein product has an exceptional multidomain structure consisting of a cluster of three epidermal growth factor homology motifs embedded between two immunoglobulinlike loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Additionally, a cDNA form lacking the first of the three epidermal growth factor homology domains was isolated, suggesting that alternative splicing creates different tie-type receptors. Cells transfected with tie cDNA expression vector produce glycosylated polypeptides of 117 kDa which are reactive to antisera raised against the tie carboxy terminus. The fie gene was located in chromosomal region ip33 to ip34. Expression of the tie gene appeared to be restricted in some cell lines; large amounts oftie mRNA were detected in endothelial cell lines and in some myeloid leukemia cell lines with erythroid and megakaryoblastoid characteristics. In addition, mRNA in situ studies further indicated the endothelial expression of the tie gene. The tie receptor tyrosine kinase may have evolved for multiple protein-protein interactions, possibly including cell adhesion to the vascular endothelium.

Long-Term and Sustained COMP-Ang1 Induces Long-Lasting Vascular Enlargement and Enhanced Blood Flow

“…Although Tie1 was isolated more than a decade ago, 18 no ligand had been found to activate it. Recently, Saharinen et al demonstrated that COMP-Ang1 stimulated Tie1 phosphorylation in cultured endothelial cells.…”

Rescue Effects and Underlying Mechanisms of IntraglandShhGene Delivery on Irradiation-Induced Hyposalivation

“…These paracrine factors downstream of Shh signaling interact with receptors on endothelial cells 40 and parasympathetic neurons and their projections 7,41 to preserve the microvasculature and parasympathetic innervation, which leads to the restoration of salivary gland function likely by improving blood supply and activating the cholinergic receptor muscarinic 1 (Chrm1)/heparin-binding EGF-like growth factor (HB-EGF) pathway with acetylcholine to promote proliferation of Chrm1 + epithelial cells in both acini and ducts of adult salivary glands. 42,43 Further investigation of other responses triggered by transient Hh activation, beneficial or harmful to restoration of the salivary gland, will improve the efficacy of this approach and facilitate its potential clinical application.…”

The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3

“…The family of fibroblast growth factor receptors (FGFRs) consist of at least four tyrosine kinases that share significant structural homology (Jaye et al, 1992;Partanen et al, 1992;Johnson and Williams, 1993).…”