TEK Tyrosine Kinase Endothelial Fc Chimera, also known as Tie-2 or CD202b, is a recombinant protein derived from mouse. It is a member of the receptor tyrosine kinase (RTK) family, which plays a crucial role in angiogenesis, vasculogenesis, and hematopoiesis. This protein is primarily expressed in endothelial cells, their progenitor cells, quiescent hematopoietic stem cells (HSCs), and a subpopulation of monocytes .
The TEK receptor tyrosine kinase is characterized by its unique structural features, including two immunoglobulin-like domains flanking three epidermal growth factor (EGF)-like domains, followed by three fibronectin type III-like repeats in the extracellular region and a split tyrosine kinase domain in the cytoplasmic region . This structure allows TEK to interact with its ligands, primarily the angiopoietin proteins.
Angiopoietin-1 (ANGPT-1) is an activator of TEK, inducing its autophosphorylation to promote, maintain, and stabilize mature blood vessels and maintain HSCs in a quiescent state . The ANGPT-1/TEK system is essential for the differentiation, proliferation, and survival of endothelial cells during embryogenesis and adult vascular homeostasis .
Upon binding with its ligand, TEK undergoes autophosphorylation at specific tyrosine residues, such as Y1106. This phosphorylation event is crucial for the recruitment and activation of downstream signaling molecules, including the downstream-of-kinase-related (Dok-R) docking protein, Grb7 adaptor protein, and tyrosine phosphatase SHP2 . These interactions regulate various cellular processes, including cell migration, survival, and angiogenesis .
TEK signaling is vital for maintaining vascular integrity and function. Overexpression or dysregulation of TEK can lead to various pathological conditions. For instance, excessive TEK signaling in the skin can result in psoriasis, characterized by epidermal hyperplasia, inflammatory cell recruitment, and altered dermal angiogenesis . Conversely, reduced TEK signaling due to overexpression of its natural antagonist, ANGPT-2, can lead to vascular defects and impaired blood vessel formation .