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

Nature Medicine
A AlbiniF Bussolino

Abstract

The HIV-1 Tat protein transactivates HIV, viral and some host cell genes. Tat can be released by infected cells and acts extracellularly in the microenvironment, regulating functions of immunocompetent and mesenchymal cells. 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 selectin). Tat induces growth of Kaposi's sarcoma (KS) spindle cells and is angiogenic in vivo and in transgenic mice10-12. We previously reported that Tat is a direct angiogenic factor 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 ac...Continue Reading

References

Jan 1, 1991·Annual Review of Biochemistry·Y N Vaishnav, F Wong-Staal
Nov 1, 1985·Annals of Internal Medicine·B SafaiB Dupont
Dec 1, 1995·Science·M FriedlanderD A Cheresh
Oct 1, 1994·Journal of Neuroimmunology·F M HofmanS M Walker
Aug 1, 1995·The Journal of Clinical Investigation·F BussolinoM R Rola-Pleszczynski
Apr 28, 1995·The Journal of Biological Chemistry·S J MandriotaM S Pepper
Oct 28, 1994·Science·S W BarnettJ A Levy
Jan 12, 1996·The Journal of Biological Chemistry·K A Thomas
Dec 1, 1996·International Journal of Cardiac Imaging·P A DoriotW Rutishauser

❮ Previous
Next ❯

Citations

Jul 22, 1998·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D Dittmer, D H Kedes
Jun 27, 2000·Journal of Cellular Physiology·F MontaldoM Prat
Apr 25, 2000·Biochemical and Biophysical Research Communications·S GhezziA Albini
Jun 21, 2005·Cellular and Molecular Neurobiology·Michal ToborekAvindra Nath
Sep 29, 2011·Neurotoxicity Research·Italo MocchettiValeriya Avdoshina
Apr 9, 2005·Experimental Neurology·William A BanksAvindra Nath
Dec 29, 1998·Immunology Today·A RubartelliM R Zocchi
Jun 6, 2003·Cancer Detection and Prevention·D BisacchiA Albini
Oct 6, 2001·Gene·L De BenedictisJ A Maier
Oct 12, 2000·Clinics in Dermatology·P Whelan, D T Scadden
Nov 27, 1999·FEMS Immunology and Medical Microbiology·R A Weiss
Aug 26, 1998·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M IurlaroA Albini
Apr 20, 2001·The International Journal of Biochemistry & Cell Biology·F BussolinoB Ensoli
Mar 20, 2001·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·M C ReM La Placa
Sep 11, 2003·The Lancet Oncology·Cecilia SgadariBarbara Ensoli
Feb 2, 2010·Expert Reviews in Molecular Medicine·Allison H Bartlett, Pyong Woo Park
Apr 18, 1998·Nature Medicine·D T Scadden
Jun 2, 1998·Kidney International·P Carmeliet, D Collen
Jul 31, 2013·Proceedings of the National Academy of Sciences of the United States of America·Tory P JohnsonAvindra Nath
Jun 25, 2009·The Journal of Biological Chemistry·Hocine YezidBruno Beaumelle
Jul 20, 2001·AIDS Research and Human Retroviruses·V CantaluppiG Camussi
Jun 14, 2003·AIDS Research and Human Retroviruses·Jørgen NyhusBirger Sørensen
Oct 27, 1997·AIDS Research and Human Retroviruses·U CavallaroJ A Maier
Oct 12, 2010·AIDS Research and Human Retroviruses·Eoin J CotterPeter P Doran
Jul 11, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·John F DeekenBruce J Dezube
Dec 22, 2011·Nucleic Acids Research·Giuseppe FiumeIleana Quinto
Sep 14, 2001·Current Opinion in Oncology·B Fingleton, L M Matrisian

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.