FLT4 : fms related receptor tyrosine kinase 4
Description
The FLT4 (fms related receptor tyrosine kinase 4) is a protein-coding gene located on chromosome 5.
The FLT4 gene provides instructions for making a protein called vascular endothelial growth factor receptor 3 (VEGFR-3), which regulates the development and maintenance of the lymphatic system. The lymphatic system produces and transports fluids and immune cells throughout the body. VEGFR-3 is turned on (activated) by two proteins called vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor D (VEGF-D). When VEGF-C and VEGF-D attach (bind) to VEGFR-3, chemical signals are produced that regulate the growth, movement, and survival of lymphatic cells.
FLT4 encodes a tyrosine-protein kinase that serves as a cell-surface receptor for VEGFC and VEGFD, playing a crucial role in adult lymphangiogenesis and the development of the vascular network and cardiovascular system during embryonic development. It promotes proliferation, survival, and migration of endothelial cells, regulating angiogenic sprouting. Activated FLT4 signaling enhances VEGFC production, creating a positive feedback loop. It modulates KDR signaling through heterodimer formation. Secreted isoform 3 acts as a decoy receptor for VEGFC/VEGFD, negatively regulating VEGFC-mediated lymphangiogenesis and angiogenesis. Isoform 1 and 2 activate various signaling cascades upon vascular growth factor binding, with isoform 2 exhibiting lower efficiency due to a truncated C-terminus lacking phosphorylation sites. It mediates activation of MAPK1/ERK2, MAPK3/ERK1, MAPK8/JUN, and AKT1 signaling pathways, phosphorylating SHC1 and PIK3R1 (the regulatory subunit of phosphatidylinositol 3-kinase). It promotes MAPK8 phosphorylation at Thr-183 and Tyr-185, and AKT1 phosphorylation at Ser-473. FLT4 interacts with VEGFC, VEGFD, PTPN14 (interaction enhanced by VEGFC stimulation), CRK, GRB2, PTK2/FAK1, SHC1, PIK3R1, and PTPN11/SHP-2. It is identified in a complex with SRC and ITGB1.
FLT4 is also known as CHTD7, FLT-4, FLT41, LMPH1A, LMPHM1, PCL, VEGFR-3, VEGFR3.
Associated Diseases
- Milroy disease
- Hemangioma, capillary infantile
- Tetralogy of Fallot
- Lymphatic malformation 1
- Congenital heart defects, multiple types, 7
