Kinase insert domain receptor (KDR)

Kinase insert domain receptor (KDR) is a type IV receptor tyrosine kinase that plays an essential role in angiogenesis and vascular development. The protein contains seven extracellular immunoglobulin-like domains, with the three most amino-terminal domains containing the necessary structural features for VEGF binding[3]. KDR functions as a cell-surface receptor for VEGFA, VEGFC, and VEGFD, promoting proliferation, survival, migration, and differentiation of endothelial cells[5]. The human KDR gene is located on chromosome 4 and encodes a protein with a molecular weight of approximately 151,527 Da and a length of 1356 amino acids[7]. The receptor contains a kinase insert domain, which is characteristic of this family of receptors. KDR has been shown to interact with several proteins including SHC2, Annexin A5, and SHC1[1]. Upon binding of vascular growth factors, KDR activates multiple signaling cascades that regulate various cellular processes. Some isoforms of KDR lack a transmembrane domain and may function as decoy receptors for VEGF ligands, potentially serving as negative regulators of lymphangiogenesis[5]. Due to its critical role in angiogenesis, KDR is an important therapeutic target for conditions involving abnormal blood vessel formation, particularly in cancer. Several inhibitors targeting KDR have been developed for potential therapeutic applications[6].

Other names

Vascular endothelial growth factor receptor 2 (VEGFR-2)Fetal Liver Kinase 1 (Flk1)CD309 (cluster of differentiation 309)Type IV receptor tyrosine kinase

Binding of vascular growth factors (VEGFA, VEGFC, VEGFD) to KDR leads to activation of several signaling cascades; Some isoforms lacking a transmembrane domain may function as decoy receptors; Forms heterodimers with FLT1 and FLT4 to modulate signaling