TEK

TEK Full Name

TEK tyrosine kinase, endothelial

TEK Introduction

TEK encodes the angiopoietin-1 receptor, a type I transmembrane protein of 1124 amino acids with a molecular weight of approximately 126 kDa. The protein belongs to the TIE family of receptor tyrosine kinases and exhibits a distinctive multidomain structure in its extracellular region: three epidermal growth factor (EGF)-like domains flanked by three immunoglobulin (Ig)-like domains, followed by three fibronectin type-III domains. This extracellular architecture mediates specific interactions with angiopoietin ligands. The protein features a single transmembrane helix and an intracellular split tyrosine kinase domain that is highly conserved among TIE family members, sharing approximately 76% sequence homology. The C-terminal tail contains a multifunctional docking site centered around tyrosine 1100 that serves as a binding platform for downstream signaling effectors.

Figure 1. Strcuture of TEK.

Vascular Signaling and Physiological Functions
TEK functions as the primary receptor for angiopoietin ligands, particularly ANGPT1, ANGPT2, and ANGPT4, playing a pivotal role in vascular development and homeostasis. Upon ligand binding, TEK undergoes autophosphorylation at specific tyrosine residues, creating docking sites for adaptor proteins including GRB2, GRB7, GRB14, SHP2, and the p85 subunit of phosphatidylinositol 3-kinase. This signaling complex activates both cell survival pathways through PI3K/AKT and migration pathways through MAPK/ERK cascades. TEK signaling exhibits context-dependent effects: in quiescent vessels, ANGPT1 promotes vascular stability by recruiting TEK to cell-cell contacts, while in migrating endothelial cells, it stimulates sprouting angiogenesis through focal adhesion complex formation. The receptor is essential for embryonic angiogenesis and heart development, and TEK-deficient mice exhibit embryonic lethality during organogenesis with impaired vascular branching and cardiac abnormalities.

Oncogenic Involvement and Therapeutic Targeting
TEK is implicated in multiple malignancies through expression in both tumor vasculature and neoplastic cells themselves. The receptor is overexpressed in the vasculature of various solid tumors including breast cancer, non-small cell lung cancer, hepatocellular carcinoma, prostate cancer, and gliomas, where it contributes to pathological angiogenesis. In glioblastoma, TEK expression correlates with tumor malignancy, regulates migration and invasion, and promotes chemoresistance through upregulation of ABC transporters. Beyond its vascular role, TEK is expressed in cancer cells of acute and chronic myeloid leukemia, malignant gliomas, thyroid cancer, gastric cancer, and endometrial carcinoma. Recent multi-omics studies in glioblastoma have identified TEK as a central regulator of endothelial-immune interactions, with TEK expression correlating with stromal activation, T-cell exclusion, and impaired immune surveillance. TEK has emerged as a druggable target, with several small molecule inhibitors in clinical development including altiratinib, CEP-11981, and DCC-2036 for solid tumors and leukemias, and AKB-9778 for peripheral arterial disease and retinopathy. The receptor is expressed predominantly in vascular endothelial cells, with high levels detected in placenta, lung, spleen, and heart, as well as in hematopoietic stem cells, pericytes, neural progenitor cells, and a subset of monocytes.

Alternate Names for TEK

TEK; TEK tyrosine kinase; endothelial; TIE2; VMCM; TIE-2; VMCM1; CD202B; angiopoietin-1 receptor; endothelial tyrosine kinase; tyrosine-protein kinase receptor TEK; tunica interna endothelial cell kinase; tyrosine-protein kinase receptor TIE-2; tyrosine kinase with Ig and EGF homology domains-2; anti-TIE-2