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The angiogenesis induced by HIV–1 Tat protein is mediated by the Flk–1/KDR receptor on vascular endothelial cells

Abstract

The HIV–1 Tat protein transactivates HIV, viral and some host cell genes1. Tat can be released by infected cells2 and acts extracellularly in the microenvironment, regulating functions of immunocompetent and mesenchymal cells3,4. One of the most striking effects of Tat is the induction of a functional program in vascular cells related to angiogenesis and inflammation (migration, proliferation and expression of plasminogen activator inhibitor–1 and E selectin5–7). Tat induces growth of Kaposi's sarcoma (KS) spindle cells8 and is angiogenic in vivo7,9 and in transgenic mice10–12. We previously reported that Tat is a direct angiogenic factor7 and noted the Tat arginine– and lysine–rich sequence is similar to that of other potent angiogenic growth factors, such as vascular endothelial growth factor–A (VEGF–A). It is possible that Tat mimics one of these factors by interacting with its growth factor tyrosine kinase receptor. Here we demonstrate that Tat specifically binds and activates the Flk–1/kinase insert domain receptor (Flk–1/KDR), a VEGF–A tyrosine kinase receptor (for review see ref. 13), and that Tat–induced angiogenesis is blocked by agents blocking the Flk–1/KDR receptor. Endothelial cell stimulation by Tat occurs in the absence of activation of FLT–1, another VEGF–A tyrosine kinase receptor.

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Albini, A., Soldi, R., Giunciuclio, D. et al. The angiogenesis induced by HIV–1 Tat protein is mediated by the Flk–1/KDR receptor on vascular endothelial cells. Nat Med 2, 1371–1375 (1996). https://doi.org/10.1038/nm1296-1371

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