Vascular Endothelial Growth Factor Receptor 2 (VEGFR2/KDR/FLK1) is the primary signaling receptor for VEGF-mediated angiogenesis. It plays crucial roles in vascular development and has been implicated in cerebrovascular pathology.
VEGFR2 (KDR/FLK1) is the primary signaling receptor for VEGF and mediates endothelial cell proliferation, migration, and survival. VEGFR2 is essential for angiogenesis. In the nervous system, VEGFR2 is expressed in neurons and mediates neuroprotective effects of VEGF. VEGFR2 signaling has been implicated in neurogenesis, synaptic plasticity, and neurodegenerative processes.
VEGFR2 is a receptor tyrosine kinase (approximately 200 kDa):
- Extracellular domain: 7 Ig-like domains (domains 2-3 bind VEGF)
- Transmembrane domain: Single-pass membrane anchor
- Intracellular domain: Tyrosine kinase domain with regulatory insertions
Key phosphorylation sites: Y951, Y996, Y1054, Y1059, Y1175, Y1214.
VEGFR2 is the main angiogenic signaling receptor:
- Endothelial proliferation: Primary mediator of VEGF-induced EC growth
- Vascular permeability: Increases endothelial barrier permeability
- Migration and survival: Chemotaxis and anti-apoptotic signaling
- Angiogenesis: Essential for new blood vessel formation
Major signaling pathways: PLCγ-PKC-MAPK, PI3K-Akt, Src-eNOS.
- Cerebrovascular dysfunction involves VEGFR2 dysregulation
- Implicated in blood-brain barrier breakdown
- Reduced signaling may contribute to hypoperfusion
- Amyloid-β affects endothelial VEGFR2
- Critical for post-ischemic angiogenesis
- Mediates revascularization following stroke
- Promotes blood-brain barrier recovery
- Target for stroke therapeutics
- Mediates trauma-induced angiogenesis
- Contributes to vascular repair
- Involved in edema formation
- VEGFR2 signaling implicated in lesion formation
- Can be activated by mutations in CCM
VEGFR2 inhibitors/activators:
- Ramucirumab: Anti-VEGFR2 antibody (cancer therapy)
- Multi-kinase inhibitors: Sorafenib, sunitinib, pazopanib
- VEGF traps: Aflibercept (binds VEGF before receptor interaction)
- VEGFR2 agonists: Being explored for ischemic conditions