Tek-gen

TEK is an acronym for "tunica interna endothelial cell kinase". This gene is located on chromosome 9p21. It codes for an endothelial receptor tyrosine kinase. Alternative splicing leads to several transcript variants. Other alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

This gene encodes a receptor(Tie2 receptor) that belongs to the Tie2 protein tyrosine kinase family. The encoded protein has a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor(EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that plays a role in embryonic vascular development. Endothelial cells, which form the inner layer of blood and lymph vessels, are important regulators of vascular function and are of central importance in the development of vascular diseases. In addition to the vascular endothelial growth factor(VEGF) receptor pathway, the angiopoietin (Ang)-Tie signaling system is a second endothelial cell-specific ligand-receptor signaling system required for embryonic cardiovascular and lymphatic development. The Ang-Tie signaling system also regulates postnatal angiogenesis, vascular remodeling, vascular permeability and inflammation to maintain vascular homeostasis in adult physiology.

Angiogenesis: Furthermore, the Tie2 receptor is an important player in angiogenesis. Mutations in the angiopoietin (Ang) Tie signaling pathway cause defects in vascular morphogenesis leading to venous malformations and primary congenital glaucoma.

Lung: Tie2 mRNA and protein are abundantly expressed in the lung.

Eye: The Ang-Tie signaling system also plays an important role in the development and function of the eye (Fodor LE et al. 2018).
Allergies: A significant association was found between the SNP rs581724 and the occurrence of allergic conjunctivitis in asthmatic children. If further studies can confirm the role of the Tie2 pathway in allergic conjunctivitis, it could represent a potential new therapeutic target in the treatment of allergic conjunctivitis (Akwii RG et al. 2021).

Mutations of the TEK gene are associated with:

• spontaneous, non-familial venous malformations. TEK mutations have also been described for the familial cases of
• Blue-Rubber-Bleb-Naevus syndrome and for primary congenital
• primary congenital glaucoma.

1. Akwii RG et al. (2021) Targeting the Angiopoietin/Tie Pathway: Prospects for Treatment of Retinal and Respiratory Disorders. Drugs 81:1731-1749.
2. Eklund L et al. (2017) Angiopoietin-Tie signaling in the cardiovascular and lymphatic systems. Clin Sci (Lond) 131:87-103.
3. Fodor LE et al. (2018) Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis. Int J Immunogenet 45:102-108

4. Teichert M et al. (2017) Pericyte-expressed Tie2 controls angiogenesis and vessel maturation. Nat Commun 8:16106.

5. Zhang Y et al. (2019) Angiopoietin-Tie Signaling Pathway in Endothelial Cells: A Computational Model. iScience 20:497-511.