Kaposi's sarcoma-associated herpesvirus interacts with EphrinA2 receptor to amplify signaling essential for productive infection

Proceedings of the National Academy of Sciences of the United States of America
Sayan ChakrabortyBala Chandran


Kaposi's sarcoma-associated herpesvirus (KSHV), etiologically associated with Kaposi's sarcoma, uses integrins (α3β1, αVβ3, and αVβ5) and associated signaling to enter human dermal microvascular endothelial cells (HMVEC-d), an in vivo target of infection. KSHV infection activated c-Cbl, which induced the selective translocation of KSHV into lipid rafts (LRs) along with the α3β1, αVβ3, and xCT receptors, but not αVβ5. LR-translocated receptors were monoubiquitinated, leading to productive macropinocytic entry, whereas non-LR-associated αVβ5 was polyubiquitinated, leading to clathrin-mediated entry that was targeted to lysosomes. Because the molecule(s) that integrate signal pathways and productive KSHV macropinocytosis were unknown, we immunoprecipitated KSHV-infected LR fractions with anti-α3β1 antibodies and analyzed them by mass spectrometry. The tyrosine kinase EphrinA2 (EphA2), implicated in many cancers, was identified in this analysis. EphA2 was activated by KSHV. EphA2 was also associated with KSHV and integrins (α3β1 and αVβ3) in LRs early during infection. Preincubation of virus with soluble EphA2, knockdown of EphA2 by shRNAs, or pretreatment of cells with anti-EphA2 monoclonal antibodies or tyrosine kinase inhibitor ...Continue Reading


Aug 26, 1998·Advances in Cancer Research·C Boshoff, R A Weiss
Jun 1, 2002·Ageing Research Reviews·Anne McArdleMalcolm Jackson
Jul 3, 2002·Nature Reviews. Molecular Cell Biology·Klas Kullander, Rüdiger Klein
Mar 5, 2003·Journal of Cell Science·Christophe DeroanneJacques Pouysségur
Jul 24, 2004·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Keith K Murai, Elena B Pasquale
Aug 26, 2004·PLoS Biology·Carsten SchnatwinkelMarino Zerial
Jun 2, 2005·Nature Reviews. Molecular Cell Biology·Elena B Pasquale
Jun 14, 2005·Nature Cell Biology·Isabelle Le BlancJ Gruenberg
Jul 7, 2005·Proceedings of the National Academy of Sciences of the United States of America·Matthew I BonaparteChristopher C Broder
Jul 22, 2005·Nature·Jim Giles
Oct 18, 2005·Nature Reviews. Molecular Cell Biology·Mirko H H Schmidt, Ivan Dikic
Mar 21, 2007·The Journal of Biological Chemistry·Letizia LanzettiSanne Jensen
Apr 11, 2007·Trends in Cell Biology·Joaquim Egea, Rüdiger Klein
Oct 12, 2007·Current Opinion in Cell Biology·Juha-Pekka HimanenDimitar B Nikolov
Dec 17, 2008·Cancer Research·Jin ChenWaldemar Debinski
May 1, 2009·Nature Cell Biology·Jason Mercer, Ari Helenius
Aug 22, 2009·Nature Reviews. Molecular Cell Biology·Alexander Sorkin, Mark von Zastrow
Aug 4, 2010·The Journal of Cell Biology·Nao Hiramoto-YamakiHironori Katoh
Nov 17, 2010·Genes & Development·Mara E Pitulescu, Ralf H Adams

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