Vascular endothelial growth factor receptor 1 and 3 (FLT1/FLT4)

Vascular endothelial growth factor receptor 1 (FLT1) and 3 (FLT4) are members of the receptor tyrosine kinase family that play essential roles in the regulation of the circulatory and lymphatic systems (UniProt P17948, P35916). FLT1 (VEGFR-1) primarily binds VEGF-A, VEGF-B, and placental growth factor (PlGF), functioning as a decoy receptor that sequesters VEGF-A to regulate angiogenesis and as a signaling receptor in inflammatory cells (Wikipedia). FLT4 (VEGFR-3) is the primary receptor for VEGF-C and VEGF-D and serves as the master regulator of lymphangiogenesis, the process of forming new lymphatic vessels (GeneCards). In cancer, both receptors are often overexpressed, contributing to tumor-induced angiogenesis and lymphangiogenesis, which facilitate tumor growth and metastasis (NIH). Consequently, they are key targets for several multi-kinase inhibitors, such as sorafenib and sunitinib, used in the treatment of solid tumors. Additionally, FLT1 is a significant biomarker in pre-eclampsia, while mutations in FLT4 are associated with hereditary lymphedema (PubMed).

Other names

VEGFR1VEGFR3Fms-like tyrosine kinase 1Fms-like tyrosine kinase 4Vascular permeability factor receptorLMPHM1FLT-1FLT-4Fms-related tyrosine kinase 1Fms-related tyrosine kinase 4

Competitive inhibition of the ATP-binding site within the intracellular tyrosine kinase domains of VEGFR-1 and VEGFR-3, leading to the suppression of downstream signaling cascades (e.g., MAPK/ERK and PI3K/AKT pathways) that drive endothelial cell survival, migration, and tube formation.