VEGFR1

VEGFR1 (Vascular Endothelial Growth Factor Receptor 1), also known as Flt-1 (Fms-like tyrosine kinase 1), is a protein that in humans is encoded by the FLT1 gene. VEGFR1 is a member of the vascular endothelial growth factor receptor (VEGFR) family, which plays a crucial role in angiogenesis, the process of new blood vessel formation from pre-existing vessels.

Structure

VEGFR1 is a receptor tyrosine kinase (RTK) that consists of an extracellular domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. The extracellular domain contains seven immunoglobulin-like loops that are responsible for binding to its ligands, primarily VEGF-A, VEGF-B, and PlGF (placental growth factor).

Function

VEGFR1 is involved in the regulation of angiogenesis and vasculogenesis. It acts as a decoy receptor for VEGF-A, sequestering it and preventing it from binding to VEGFR2, which is the primary mediator of VEGF-induced angiogenic signaling. Despite its role as a decoy receptor, VEGFR1 also has signaling capabilities that can influence cell migration, survival, and differentiation.

Ligand Binding

VEGFR1 binds to VEGF-A with high affinity, but its kinase activity is weaker compared to VEGFR2. The binding of VEGF-B and PlGF to VEGFR1 can modulate the availability of VEGF-A for VEGFR2, thus indirectly influencing angiogenic signaling.

Signaling Pathways

Upon ligand binding, VEGFR1 undergoes dimerization and autophosphorylation, activating downstream signaling pathways. These pathways include the PI3K/AKT pathway, which is involved in cell survival, and the MAPK/ERK pathway, which is associated with cell proliferation and migration.

Clinical Significance

VEGFR1 is implicated in various pathological conditions, including cancer, where it can contribute to tumor angiogenesis and metastasis. It is also involved in inflammatory diseases and ocular disorders such as age-related macular degeneration (AMD).

Therapeutic Target

VEGFR1 is a target for anti-angiogenic therapies. Inhibitors of VEGFR1, such as monoclonal antibodies and small molecule tyrosine kinase inhibitors, are being developed to treat cancers and other diseases characterized by excessive angiogenesis.

Research and Development

Ongoing research is focused on understanding the precise role of VEGFR1 in different tissues and its potential as a biomarker for disease progression and treatment response. Studies are also exploring the development of selective VEGFR1 inhibitors that can provide therapeutic benefits with minimal side effects.

Also see

• VEGFR2
• VEGF-A
• Angiogenesis
• Receptor tyrosine kinase
• Cancer therapy