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Angiopoietin/Tie

Angiopoietin/Tie

Sino Biological offers a comprehensive set of tools for Angiopoietin/Tie system related research, including recombinant proteins, antibodies, ELISA kits and gene cDNA clones. Angiopoietins are growth factors that promote angiogenesis, the process of new blood vessel formation. Angiopoietins bind and activate the tie receptors, tie1 and tie2, which are cell-surface receptor tyrosine kinases. Angiopoietin-Tie signalling is essential during embryonic vessel assembly and maturation, and functions as a key regulator of adult vascular homeostasis. As is supported by clinical studies and studies in animal models, Angiopoietin-Tie signaling contributes to disease pathogenesis.

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    Angiopoietin/Tie Background

    Angiopoietins are growth factors that promote angiogenesis, the process of new blood vessel formation. There are now four identified angiopoietins: Ang1, Ang2, Ang3, Ang4. Angiopoietins are 70-kDa glycoproteins that contain an amino-terminal angiopoietin-specific domain, a coiled-coil domain, a linker peptide and a carboxyl-terminal fibrinogen homology domain. In addition, 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.

    Angiopoietin-Tie signalling is essential during embryonic vessel assembly and maturation, and functions as a key regulator of adult 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.

    Angiopoietin/Tie References

      1. Shim WS, et al. (2007) Angiopoietin: a TIE(d) balance in tumor angiogenesis. Mol Cancer Res. 5(7):655-65.
      2. Davis B, et al. (2007) Podocyte-specific expression of angiopoietin-2 causes proteinuria and apoptosis of glomerular endothelia. J Am Soc Nephrol. 18(8):2320-9.
      3. Campean V, et al. (2008) Angiopoietin 1 and 2 gene and protein expression is differentially regulated in acute anti-Thy1.1 glomerulonephritis. Am J Physiol Renal Physiol. 294(5):F1174-84.
      4. van Meurs M, et al. (2009) Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target? Crit Care. 13(2):207.
      5. van der Heijden M,et al. (2009) The angiopoietin-Tie2 system as a therapeutic target in sepsis and acute lung injury. Expert Opin Ther Targets. 13(1):39-53.