VEGFR3

Vascular Endothelial Growth Factor Receptor 3 (VEGFR3)

Vascular Endothelial Growth Factor Receptor 3 (VEGFR3), also known as Fms-like tyrosine kinase 4 (FLT4), is a receptor tyrosine kinase that plays a crucial role in the regulation of lymphangiogenesis, the formation of lymphatic vessels from pre-existing lymphatic endothelium. VEGFR3 is primarily expressed in the lymphatic endothelium and is activated by its ligands, VEGF-C and VEGF-D.

Structure

VEGFR3 is a member of the VEGF receptor family, which includes VEGFR1 and VEGFR2. It is a transmembrane protein composed of an extracellular ligand-binding 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, VEGF-C and VEGF-D.

Function

VEGFR3 is essential for the development and maintenance of the lymphatic vascular system. Upon binding to its ligands, VEGFR3 undergoes dimerization and autophosphorylation, which activates downstream signaling pathways. These pathways include the PI3K/Akt pathway, which promotes cell survival, and the MAPK/ERK pathway, which is involved in cell proliferation and migration.

Role in Lymphangiogenesis

VEGFR3 is a key regulator of lymphangiogenesis. During embryonic development, VEGFR3 is expressed in the venous endothelium and is crucial for the formation of the primary lymphatic structures. In adults, VEGFR3 continues to play a role in the remodeling and maintenance of the lymphatic system, as well as in pathological conditions such as cancer metastasis and lymphedema.

Role in Disease

VEGFR3 has been implicated in various diseases, particularly those involving the lymphatic system. Overexpression of VEGFR3 and its ligands has been observed in several types of cancer, where it contributes to tumor lymphangiogenesis and metastasis. Inhibitors targeting VEGFR3 are being investigated as potential therapeutic agents for cancer treatment.

Clinical Significance

The expression and activity of VEGFR3 are of clinical interest due to their involvement in cancer progression and other lymphatic disorders. Targeting VEGFR3 with specific inhibitors or monoclonal antibodies is a promising strategy for the treatment of diseases characterized by abnormal lymphangiogenesis.

Research and Development

Ongoing research is focused on understanding the detailed mechanisms of VEGFR3 signaling and its interactions with other molecular pathways. This research aims to develop novel therapeutic approaches for diseases associated with lymphatic dysfunction.

Also see

• VEGF-C
• VEGF-D
• Lymphangiogenesis
• Receptor tyrosine kinase
• Cancer metastasis