Abstract
The Tie [tyrosine kinase with immunoglobulin and epidermal growth factor (EGF) homology domains] receptors, Tie-1 and Tie-2, have been found to be localized primarily to the endothelial and hematopoietic cells in all organisms (human, mouse, rat, zebrafish) that have been examined (Wilks, 1989;Dumont et al., 1992;Iwama, et al., 1993;Maisonpierre et al., 1993;Sato et al., 1993;Lyons et al., 1998). The only other receptors that share this feature are those that bind and are activated by the (VEGF) family members (discussed in the previous chapter). Tie-1 and Tie-2 are large (-160 kDa) multidomain proteins that are highly homologous. The rat genes share 32% sequence identity in their extracellular regions and 79% sequence identity in their intracellular regions (Maisonpierre et al., 1997). The mouse genes are both on chromosome 4, separated by only 12.2 centimorgans (cM), while the human Tie-1 gene is on 1p33–34, which is a syntenic location (Korhonen et al., 1994). Human Tie-2 is on 9p21. The ligands for Tie-2, the angiopoietins, comprise a unique family of proteins, the first member of which was cloned only a few years ago (Davis et al., 1996;Maisonpierre et al., 1997;Valenzuela et al., 1999). All the angiopoietins are highly homologous to each other; angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are —60% identical in their amino acid sequence; angiopoietin-3 and -4 (Ang3 and 4) show —54% identity to Ang1 (Maisonpierre et al., 1997;Valenzuela et al., 1999). They have diverged enough to serve different functions and to reside on different chromosomes.15 (syntenic); for Ang2, the human gene is on 8p21 and the mouse gene on chromosome 8 (syn-tenic), whereas human Ang4 is on 20p13 and mouse Ang3 is on chromosome 2 (which are also syntenic) (Valenzuela et aI., 1999). So far, there are no definitive ligands for Tie-I.
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Suri, C., Yancopoulos, G.D. (2002). The Ties That Bind: Emerging Concepts About the Structure and Function of Angiopoietins and Their Receptors in Angiogenesis. In: Tomanek, R.J. (eds) Assembly of the Vasculature and Its Regulation. Cardiovascular Molecular Morphogenesis. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4612-0109-0_3
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DOI: https://doi.org/10.1007/978-1-4612-0109-0_3
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