TIE1

Fig1. The structure of Tie receptor Tie. (Ping Yang, 2015)

What is TIE1 protein?

TIE1 (tyrosine kinase with immunoglobulin like and EGF like domains 1) gene is a protein coding gene which situated on the short arm of chromosome 1 at locus 1p34. This gene encodes a member of the tyrosine protein kinase family. The encoded protein plays a critical role in angiogenesis and blood vessel stability by inhibiting angiopoietin 1 signaling through the endothelial receptor tyrosine kinase Tie2. Ectodomain cleavage of the encoded protein relieves inhibition of Tie2 and is mediated by multiple factors including vascular endothelial growth factor. The TIE1 protein is consisted of 1138 amino acids and its molecular mass is approximately 125.1 kDa.

What is the function of TIE1 protein?

TIE1 protein is a receptor tyrosine kinase mainly expressed in vascular endothelial cells. After binding to its ligand ANGIOPOIETIN, TIE1 protein is involved in regulating physiological processes such as angiogenesis, vascular stability and vascular permeability. Specifically, TIE1 protein, by binding to ANGIOPOIETIN 1, can promote the recruitment of vascular smooth muscle cells and the stability of vascular basement membrane, thereby maintaining the resting state of blood vessels; Binding to ANGIOPOIETIN 2 disrupts vascular stability and increases vascular permeability, which plays an important role in pathological processes such as inflammation and tumor growth.

TIE1 Related Signaling Pathway

TIE1 is a tyrosine kinase receptor that is mainly expressed in vascular endothelial cells. It interacts with its ligand Angiopoietin to regulate angiogenesis and maturation. The Ang1-TIE2-TEK signaling pathway is the main signaling pathway related to TIE1 protein. When Ang1 binds to TIE2, it can activate TEK (also known as TIE1), which promotes the survival, stability, and maturation of endothelial cells. In addition, this signaling pathway also interacts with a variety of other signaling pathways, such as PI3K/AKT, MAPK, etc., to further regulate cell function.

TIE1 Related Diseases

TIE1 protein abnormalities may lead to a range of vascular related diseases, such as tumors, diabetic retinopathy, atherosclerosis, etc. In addition, the TIE1 protein is also critical for the regulation of angiogenesis during embryonic development, so its abnormality may be associated with certain congenital vascular malformations.

Bioapplications of TIE1

TIE1 protein is a molecular target with wide application prospects in tumor therapy, immune regulation, cardiovascular system disease treatment and other fields. Some anti-tumor drugs use it to block the development of tumors; The development of immunosuppressants targeting it can effectively delay the development of inflammation.

Case Study 1: Tomoka Misawa, 2021

Ovarian cancer is the most lethal gynecologic malignancy due to the tumor's acquisition of chemoresistance to platinum-based chemotherapy. To solve this problem, we conducted RNAi-based large-scale screening and determined that tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE-1) is a key molecule involved in the platinum resistance of ovarian cancer cells. Recently, a variety of studies have investigated that small extracellular vesicles (sEVs) contribute to the communication between cancer cells, including the development of chemoresistance in ovarian cancer.

TIE-1-overexpressed TOV112D cells, termed TOV112DTIE-1 cells, were established, and sEVs were isolated from TOV112DTIE-1 cells supernatants by ultracentrifugation. The researchers assessed cisplatin sensitivity in recipient cells with TOV112DTIE-1-derived sEVs by cell-Titer Glo kit. They also asked whether sEV-derived TIE-1 suppressed the DNA damage response in recipient cells and evaluated the DNA damage response by counting cells positive for DNA damage foci. TIE-1 was contained within sEVTIE-1 derived from the cellular supernatant of TOV112DTIE-1. They showed that sEV-derived TIE-1 decreased chemosensitivity to cisplatin by suppressing the DNA damage response in recipient cells.

Fig1. Immunoblotting for TIE-1, V5 and β-actin in whole cell lysates.

Fig2. Immunoblotting of TIE-1, V5, CD81 and CD9 (exosome marker) in sEVTIE-1.

Case Study 2: Julie Garcia, 2012

Endothelial-mesenchymal transition (EndMT) has a significant role in embryonic heart formation and in various pathologies. However, the molecular mechanisms that regulate EndMT induction remain to be elucidated. The researchers show that suppression of receptor tyrosine kinase Tie1 but not Tie2 induces human endothelial cells to undergo EndMT and that Slug deficiency reverts this process. They find that Erk1/2, Erk5 and Akt cascades control Slug promoter activity induced by Tie1 deficiency. Interestingly, EndMT is present in human pancreatic tumour. They propose that EndMT associated with Tie1 downregulation participates in the pathological development of stroma observed in tumours.

Fig3. Tie1 (left panel) or Tie2 (right panel) siRNA suppresses mRNA and protein expression.

Fig4. Tie1 silencing increases Slug expression. HMVECs were transfected with Tie1 or Ctrl siRNA.

TIE1 has several biochemical functions, for example, ATP binding,protein binding,transmembrane receptor protein tyrosine kinase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by TIE1 itself. We selected most functions TIE1 had, and list some proteins which have the same functions with TIE1. You can find most of the proteins on our site.

TIE1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with TIE1 here. Most of them are supplied by our site. Hope this information will be useful for your research of TIE1.

KRT40;RBPMS;PSG5;MDFI;PTPRC;PTPRG;Dlg4;PTPRJ;HSP90AB1;CDC37