FMO3

FLT1

The FLT1 gene, also known as Fms-related tyrosine kinase 1, is a crucial component in the vascular endothelial growth factor (VEGF) receptor family. It plays a significant role in angiogenesis, the process by which new blood vessels form from pre-existing vessels, and is vital for both normal development and pathological conditions such as cancer.

Structure

The FLT1 gene is located on chromosome 13q12 and encodes a protein that is a member of the class III receptor tyrosine kinase family. The FLT1 protein consists of an extracellular domain, a transmembrane domain, and an intracellular tyrosine kinase domain. The extracellular domain contains seven immunoglobulin-like loops that are responsible for binding to its ligands, VEGF-A, VEGF-B, and placental growth factor (PlGF).

Function

FLT1 functions primarily as a receptor for VEGF and PlGF. Upon ligand binding, FLT1 undergoes dimerization and autophosphorylation, activating downstream signaling pathways that regulate endothelial cell proliferation, migration, and survival. These processes are essential for angiogenesis and vascular permeability.

FLT1 also exists in a soluble form, known as sFLT1, which acts as a decoy receptor by sequestering VEGF and PlGF, thus inhibiting their interaction with other VEGF receptors such as KDR (VEGFR-2). This mechanism is particularly important in regulating angiogenesis and maintaining vascular homeostasis.

Clinical Significance

Abnormal FLT1 signaling is implicated in various diseases. Overexpression of FLT1 is associated with tumor angiogenesis, contributing to cancer progression and metastasis. Inhibitors targeting FLT1 and its ligands are being explored as therapeutic strategies in oncology.

In preeclampsia, a pregnancy-related disorder, elevated levels of sFLT1 are observed, leading to reduced availability of free VEGF and PlGF, which contributes to endothelial dysfunction and the clinical manifestations of the disease.

Research and Therapeutic Implications

FLT1 is a target for anti-angiogenic therapies. Drugs such as bevacizumab, a monoclonal antibody against VEGF, indirectly affect FLT1 activity by reducing the availability of its ligands. Research is ongoing to develop more specific FLT1 inhibitors that could provide therapeutic benefits in cancer and other angiogenesis-related diseases.

Also see

• VEGF
• Angiogenesis
• Receptor tyrosine kinase
• Preeclampsia
• Cancer therapy