Molecular Cancer Biology Laboratory, and the Ludwig Institute for Cancer Research, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland

Correspondence to: T V Petrova, Molecular Cancer Biology Laboratory, and the Ludwig Institute for Cancer Research, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland

VEGFR-1 (Flt-1), VEGFR-2 (KDR) and VEGFR-3 (Flt4) are endothelial specific receptor tyrosine kinases, regulated by members of the vascular endothelial growth factor family. VEGFRs are indispensable for embryonic vascular development, and are involved in the regulation of many aspects of physiological and pathological angiogenesis. VEGF-C and VEGF-D, as ligands for VEGFR-3 are also capable of stimulating lymphangiogenesis and at least VEGF-C can enhance lymphatic metastasis. Recent studies have shown that missense mutations within the VEGFR-3 tyrosine kinase domain are associated with human hereditary lymphedema, suggesting an important role for this receptor in the development of the lymphatic vasculature. Oncogene (2000) 19, 5598-5605.

angiogenesis; endothelial cells; receptor tyrosine kinases; signal transduction; VEGF receptors; VEGF

eNOS, endothelial nitric oxide synthase; FAK, focal adhesion kinase; HUVE, human umbilical vein endothelial; IP3, inositol-3-phosphate; MAPK, mitogen activated protein kinase; PI3-K, phosphatidylinositol 3-kinase; PKC, protein kinase C; PLC, phospholipase C; PlGF, placenta growth factor; RTK, receptor tyrosine kinase; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor