Document 0072
 DOCN  M9650072
 TI    HIV-tat protein is a heparin-binding angiogenic growth factor.
 DT    9605
 AU    Albini A; Benelli R; Presta M; Rusnati M; Ziche M; Rubartelli A;
       Paglialunga G; Bussolino F; Noonan D; Istituto Nazionale per la Ricerca
       sul Cancro, Genova, Italy.
 SO    Oncogene. 1996 Jan 18;12(2):289-97. Unique Identifier : AIDSLINE
       PIR/A23553
 AB    Transgenic animal studies have linked the expression of the HIV-1 tat
       gene to the appearance of Kaposi's sarcoma (KS)-like lesions. We have
       recently shown that recombinant tat is angiogenic in vivo, and that tat
       angiogenic response is enhanced by heparin. Also in the rabbit cornea
       model, recombinant HIV-1 tat alone is poorly angiogenic, but gives a
       good response when combined with heparin. Like many angiogenic growth
       factors, tat has a basic domain similar to that of several heparin
       binding angiogenic factors, including FGF, VEGF and HGF, suggesting that
       this region is important in endothelial cell activation. We show that
       tat binds heparin sepharose with a high affinity, similar to bFGF.
       Binding of tat to the cell surface is also modulated by heparin.
       Biological activities of tat, such as induction of endothelial cell
       growth, migration and invasion in vitro are all enhanced by low
       concentrations and inhibited by high concentrations of heparin, as has
       been shown for other heparin-binding angiogenic factors. Heparan sulfate
       is also effective, whereas the unsulfated polysaccharide K5 does not
       enhance tat activity. Furthermore, a peptide encompassing the tat basic
       domain is able to induce growth and migration of endothelial cells,
       while an adjacent peptide is not. Our data indicate that the tat basic
       domain plays a key role in its vascular cell activation properties, and
       strongly suggest that extracellular HIV-tat is essentially a 'new'
       heparin-binding angiogenic factor.
 DE    Amino Acid Sequence  Angiogenesis Factor/*METABOLISM  Animal  Cells,
       Cultured  Endothelium, Vascular/DRUG EFFECTS  Gene Products,
       tat/*METABOLISM/PHARMACOLOGY  Heparin/*METABOLISM/PHARMACOLOGY  Human
       Molecular Sequence Data  Rabbits  Support, Non-U.S. Gov't  JOURNAL
       ARTICLE

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