As members of growth factor receptors, Tie is the cognate receptor for angiopoietin. The Tie1 and Tie2 receptor tyrosine kinases form a distinct subfamily characterized by their unique extracellular domains. Together with the angiopoietin growth factors, the Tie receptors form an endothelial specific signaling pathway with important functions in the regulation of lymphatic and cardiovascular development and vascular homeostasis.
As is supported by clinical studies and studies in animal models, Angiopoietin-Tie signaling contributes to disease pathogenesis. In mice, Angiopoietin-2 over-expression in glomeruli causes proteinuria and apoptosis of glomerular endothelial cells. In a rat model of glomerulonephritis, Tie2 is over-expressed by endothelial cells, and Angiopoietin-1 and Angiopoietin-2 are over-expressed by podocytes in a time-dependent manner during the repair phase. Angiopoietin-Tie2 system has been also discovered as potential therapeutic target in sepsis and acute lung injury. A number of proteins are found closely related to angiopoietins, including ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL5, ANGPTL6, and ANGPTL7. Angiopoietins bind and activate the tie receptors, tie1 and tie2, which are cell-surface receptor tyrosine kinases. Angiopoietin-1 and Angiopoietin-2 bind to Tie2 after polymerization of at least four Angiopoietin-1 and two Angiopoietin-2 subunits. The dissimilarity between Angiopoietin-1 and Angiopoietin-2 signaling lies in subtle differences in the receptor binding domain that lead to distinct intracellular actions of the receptor; differential cellular handling of both receptor and ligands after binding and signaling initiation may also play a role. Ligand binding to the extracellular domain of Tie2 results in receptor dimerization, autophosphorylation and docking of adaptors, and coupling to intracellular signaling pathways. PI3K/Akt and NF-kB pathways are regulated by Tie2.
Sino Biological offers a comprehensive set of tools for Angiopoietin/Tie system related research, including recombinant proteins, antibodies, ELISA kits and gene cDNA clones.