FLT1
Description
The FLT1 (fms related receptor tyrosine kinase 1) is a protein-coding gene located on chromosome 13.
Vascular endothelial growth factor receptor 1 is a protein that in humans is encoded by the FLT1 gene.
== Function == FLT1 is a member of VEGF receptor gene family. It encodes a receptor tyrosine kinase which is activated by VEGF-A, VEGF-B, and placental growth factor. The sequence structure of the FLT1 gene resembles that of the FMS (now CSF1R) gene; hence, Yoshida et al. (1987) proposed the name FLT as an acronym for FMS-like tyrosine kinase. The ablation of VEGFR1 by chemical and genetic means has also recently been found to augment the conversion of white adipose tissue to brown adipose tissue as well as increase brown adipose angiogenesis in mice. Functional genetic variation in FLT1 (rs9582036) has been found to affect non-small cell lung cancer survival.
== Interactions == FLT1 has been shown to interact with PLCG1 and vascular endothelial growth factor B (VEGF-B).
FLT1, also known as VEGFR-1, is a tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB, and PGF. It plays a critical role in the development of embryonic vasculature and regulates angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. FLT1 also functions as a positive regulator of postnatal retinal hyaloid vessel regression and may act as a negative regulator of embryonic angiogenesis by inhibiting excessive endothelial cell proliferation. While FLT1 can promote endothelial cell proliferation, survival, and angiogenesis in adulthood, its role in promoting cell proliferation appears to be cell-type specific. FLT1 promotes PGF-mediated proliferation of endothelial cells and the proliferation of some cancer cell types, but it does not promote the proliferation of normal fibroblasts in vitro. FLT1 has a high affinity for VEGFA and relatively low protein kinase activity, suggesting it may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Additionally, FLT1 modulates KDR signaling by forming heterodimers with KDR. Ligand binding to FLT1 activates various signaling cascades, including the activation of PLCG, which leads to the production of diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. FLT1 also mediates the phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, activating phosphatidylinositol kinase and downstream signaling pathways. Furthermore, FLT1 mediates the activation of MAPK1/ERK2, MAPK3/ERK1, and the MAP kinase signaling pathway, as well as the AKT1 signaling pathway. FLT1 phosphorylates SRC and YES1, and may also phosphorylate CBL. It promotes the phosphorylation of AKT1 at 'Ser-473' and PTK2/FAK1. FLT1 phosphorylates PLCG and may function as a decoy receptor for VEGFA. FLT1 possesses a truncated kinase domain, increasing the phosphorylation of SRC at 'Tyr-418' by unknown means and promoting tumor cell invasion. FLT1 interacts with VEGFA, VEGFB, and PGF. It exists as a monomer in the absence of bound VEGFA, VEGFB, or PGF, but forms a homodimer in the presence of these ligands. FLT1 can also form a heterodimer with KDR. When tyrosine phosphorylated, FLT1 interacts with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG, PSEN1, and PTPN11. It likely also interacts with PTPRB and interacts with RACK1. FLT1 has been identified in a complex with CBL and CD2AP.
FLT1 is also known as FLT, FLT-1, VEGFR-1, VEGFR1.
