Flk1VEGFR2

Flk1VEGFR2, also known as Flk-1 in mice and VEGFR-2 or KDR in humans, is a receptor tyrosine kinase that serves as the primary signaling receptor for vascular endothelial growth factor (VEGF). It is chiefly expressed on vascular endothelial cells and plays a central role in the regulation of angiogenesis and vasculogenesis. Flk1/KDR is a key component of the VEGF signaling axis that connects extracellular VEGF ligands to intracellular cascades regulating endothelial cell behavior.

The protein structure of Flk1/VEGFR-2 includes an extracellular domain with seven immunoglobulin-like motifs for ligand binding, a single transmembrane region, and an intracellular tyrosine kinase domain responsible for signal transduction after activation. The main physiological ligand is VEGF-A, though VEGF-E and, to a lesser extent, other VEGF family members can interact with VEGFR-2 under certain conditions. Ligand binding induces receptor dimerization and autophosphorylation on multiple tyrosine residues, which in turn recruits signaling proteins such as PLCγ, PI3K–AKT, and the Ras–MAPK pathways. These cascades promote endothelial cell proliferation, migration, survival, and increased vascular permeability.

Flk1/VEGFR-2 is essential for embryonic vascular development; loss of function disrupts vasculogenesis and is typically embryonically lethal in model organisms. In adults, the receptor contributes to physiological angiogenesis during wound healing and reproductive cycles, and it mediates pathological angiogenesis in diseases such as cancer. Because of its pivotal role in blood vessel formation, VEGFR-2 is a major target for anti-angiogenic therapies, including receptor-targeted antibodies and small-molecule inhibitors. Flk1+ cells are also used as markers of endothelial lineage in developmental studies.