title: Binding of ATP to vascular endothelial growth factor isoform VEGF-A165 is essential for inducing proliferation of human umbilical vein endothelial cells.
abstract: BACKGROUND
  ATP binding is essential for the bioactivity of several growth factors including nerve growth factor, fibroblast growth factor-2 and brain-derived neurotrophic factor. Vascular endothelial growth factor isoform 165 (VEGF-A(165)) induces the proliferation of human umbilical vein endothelial cells, however a dependence on ATP-binding is currently unknown. The aim of the present study was to determine if ATP binding is essential for the bioactivity of VEGF-A(165).
  
  
  RESULTS
  We found evidence that ATP binding to VEGF-A(165) induced a conformational change in the secondary structure of the growth factor. This binding appears to be significant at the biological level, as we found evidence that nanomolar levels of ATP (4-8 nm) are required for the VEGF-A(165)-induced proliferation of human umbilical vein endothelial cells. At these levels, purinergic signaling by ATP via P2 receptors can be excluded. Addition of alkaline phosphate to cell culture lowered the ATP concentration in the cell culture medium to 1.8 nM and inhibited cell proliferation.
  
  
  CONCLUSIONS
  We propose that proliferation of endothelial cells is induced by a VEGF-A(165)-ATP complex, rather than VEGF-A(165) alone.
authors: Institut für Pharmazeutische und Medizinische Chemie, Hittorfstrasse 58-62, 48149 Münster, Germany.
authors: Ronald E
authors: RE
authors: Gast
authors: Simone
authors: S
authors: König
authors: Karsten
authors: K
authors: Rose
authors: Katja B
authors: KB
authors: Ferenz
authors: Josef
authors: J
authors: Krieglstein
references: Biochem Biophys Res Commun. 2006 Feb 17;340(3):836-9
references: 16386708
references: Pharm Res. 2001 Oct;18(10):1455-60
references: 11697472
references: J Biol Chem. 1992 Dec 25;267(36):26031-7
references: 1464614
references: Biochem Biophys Res Commun. 1989 Jun 15;161(2):851-8
references: 2735925
references: J Biol Chem. 2003 May 9;278(19):17164-9
references: 12598527
references: Lab Invest. 1995 Jun;72(6):615-8
references: 7540232
references: J Am Soc Mass Spectrom. 2008 Jan;19(1):91-5
references: 18055212
references: Arch Biochem Biophys. 1997 Aug 1;344(1):103-13
references: 9244387
references: Semin Thromb Hemost. 2005 Apr;31(2):139-49
references: 15852217
references: Nature. 1996 Apr 4;380(6573):435-9
references: 8602241
references: Arterioscler Thromb Vasc Biol. 2002 Mar 1;22(3):364-73
references: 11884276
references: Nat Med. 1999 May;5(5):495-502
references: 10229225
references: Biochem Biophys Res Commun. 1992 Sep 30;187(3):1579-86
references: 1417831
references: J Biol Chem. 2004 Aug 20;279(34):35679-86
references: 15175347
references: Genes Dev. 2002 Oct 15;16(20):2684-98
references: 12381667
references: J Biotechnol. 2010 Jan 1;145(1):54-9
references: 19836424
references: J Biol Chem. 1996 Mar 29;271(13):7788-95
references: 8631822
references: J Biol Chem. 1997 Mar 14;272(11):7151-8
references: 9054410
references: Neurochem Int. 2007 Jul;51(1):25-31
references: 17524524
references: Endocr Rev. 1997 Feb;18(1):4-25
references: 9034784
references: Endocrinology. 1992 Jul;131(1):254-60
references: 1612003
references: Science. 1989 Dec 8;246(4935):1306-9
references: 2479986
references: J Control Release. 2000 Oct 3;69(1):149-58
references: 11018553
references: Neurochem Int. 2010 Jan;56(2):276-84
references: 19897001
references: Biochemistry. 1994 Apr 5;33(13):3831-40
references: 8142385
references: Clin Sci (Lond). 1999 Sep;97(3):303-12
references: 10464055
references: J Immunol. 1994 Apr 15;152(8):4149-56
references: 7511670
references: J Biochem. 2008 Sep;144(3):343-7
references: 18511454
references: Trends Pharmacol Sci. 2006 Mar;27(3):166-76
references: 16487603
references: BMC Biochem. 2011 Mar 29;12:14
references: 21447157
references: Angiogenesis. 2008;11(2):169-82
references: 18071915
references: Br J Cancer. 2009 May 5;100(9):1465-70
references: 19367276
references: Invest Ophthalmol Vis Sci. 1999 Mar;40(3):752-9
references: 10067980
references: J Exp Med. 1992 Nov 1;176(5):1375-9
references: 1402682
references: Neuroscience. 2009 Dec 29;164(4):1695-700
references: 19782732
references: Neurochem Int. 2006 Jan;48(2):131-7
references: 16242215
references: J Biochem Biophys Methods. 1994 Apr;28(3):239-42
references: 8064118
references: J Cell Biochem. 2002;85(2):357-68
references: 11948691
references: Science. 1992 Feb 21;255(5047):989-91
references: 1312256
references: Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12081-7
references: 9342366
references: J Exp Med. 1994 Sep 1;180(3):1141-6
references: 8064230
references: Cell. 1998 Mar 20;92(6):735-45
references: 9529250