@article {45,
	title = {Structural determinants of vascular endothelial growth factor-D receptor binding and specificity},
	journal = {Blood},
	volume = {117},
	year = {2011},
	month = {2011/Feb/},
	pages = {1507 - 15},
	abstract = {Vascular endothelial growth factors (VEGFs) and their tyrosine kinase receptors (VEGFR-1-3) are central mediators of angiogenesis and lymphangiogenesis. VEGFR-3 ligands VEGF-C and VEGF-D are produced as precursor proteins with long N- and C-terminal propeptides and show enhanced VEGFR-2 and VEGFR-3 binding on proteolytic removal of the propeptides. Two different proteolytic cleavage sites have been reported in the VEGF-D N-terminus. We report here the crystal structure of the human VEGF-D Cys117Ala mutant at 2.9 {\r A} resolution. Comparison of the VEGF-D and VEGF-C structures shows similar extended N-terminal helices, conserved overall folds, and VEGFR-2 interacting residues. Consistent with this, the affinity and the thermodynamic parameters for VEGFR-2 binding are very similar. In comparison with VEGF-C structures, however, the VEGF-D N-terminal helix was extended by 2 more turns because of a better resolution. Both receptor binding and functional assays of N-terminally truncated VEGF-D polypeptides indicated that the residues between the reported proteolytic cleavage sites are important for VEGF-D binding and activation of VEGFR-3, but not of VEGFR-2. Thus, we define here a VEGFR-2-specific form of VEGF-D that is angiogenic but not lymphangiogenic. These results provide important new insights into VEGF-D structure and function.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/21148085},
	author = {Lepp{\"a}nen, Veli-Matti and Jeltsch, Michael and Anisimov, Andrey and Tvorogov, Denis and Aho, Kukka and Kalkkinen, Nisse and Toivanen, Pyry and Yl{\"a}-Herttuala, Seppo and Ballmer-Hofer, Kurt and Alitalo, Kari}
}
@article {32,
	title = {Vascular endothelial growth factor (VEGF)/VEGF-C mosaic molecules reveal specificity determinants and feature novel receptor binding patterns},
	journal = {J Biol Chem},
	volume = {281},
	year = {2006},
	month = {2006/Apr/},
	pages = {12187 - 95},
	abstract = {Vascular 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.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/16505489},
	author = {Jeltsch, Michael and Karpanen, Terhi and Strandin, Tomas and Aho, Kukka and Lankinen, Hilkka and Alitalo, Kari}
}
