01519nas a2200193   4500008004100000245014600041210006900187260001400256300001500270490000800285520086800293100002101161700002001182700002001202700001501222700002101237700001801258856004901276       2006                        eng d00aVascular endothelial growth factor (VEGF)/VEGF-C mosaic molecules reveal specificity determinants and feature novel receptor binding patterns0 aVascular endothelial growth factor VEGFVEGFC mosaic molecules re  c2006/Apr/  a12187 - 950 v2813 aVascular endothelial growth factors (VEGFs) and their receptors play key roles in angiogenesis and lymphangiogenesis. VEGF activates VEGF receptor-1 (VEGFR-1) and VEGFR-2, whereas VEGF-C activates VEGFR-2 and VEGFR-3. We have created a library of VEGF/VEGF-C mosaic molecules that contains factors with novel receptor binding profiles, notably proteins binding to all three VEGF receptors ("super-VEGFs"). The analyzed super-VEGFs show both angiogenic and lymphangiogenic effects in vivo, although weaker than the parental molecules. The composition of the VEGFR-3 binding molecules and scanning mutagenesis revealed determinants of receptor binding and specificity. VEGFR-2 and VEGFR-3 showed striking differences in their requirements for VEGF-C binding; extracellular domain 2 of VEGFR-2 was sufficient, whereas in VEGFR-3, both domains 1 and 2 were necessary.1 aJeltsch, Michael1 aKarpanen, Terhi1 aStrandin, Tomas1 aAho, Kukka1 aLankinen, Hilkka1 aAlitalo, Kari  uhttp://view.ncbi.nlm.nih.gov/pubmed/16505489