Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network

Eldad Tzahar, James D. Moyer, Hadassa Waterman, Elsa G. Barbacci, Jing Bao, Gil Levkowitz, Maya Shelly, Sabrina Strano, Ronit Pinkas-Kramarski, Jacalyn H. Pierce, Glenn C. Andrews, Yosef Yarden

Research output: Contribution to journalArticle

Abstract

Virulence of poxviruses, the causative agents of smallpox, depends on virus-encoded growth factors related to the mammalian epidermal growth factor (EGF). Here we report that the growth factors of Shope fibroma virus, Myxoma virus and vaccinia virus (SFGF, MGF and VGF) display unique patterns of specificity to ErbB receptor tyrosine kinases; whereas SFGF is a broad-specificity ligand, VGF binds primarily to ErbB-1 homodimers, and the exclusive receptor for MGF is a heterodimer comprised of ErbB-2 and ErbB-3. In spite of 10- to 1000-fold lower binding affinity to their respective receptors, the viral ligands are mitogenically equivalent or even more potent than their mammalian counterparts. This remarkable enhancement of cell growth is due to attenuation of receptor degradation and ubiquitination, which leads to sustained signal transduction. Our results imply that signal potentiation and precise targeting to specific receptor combinations contribute to cell transformation at sites of poxvirus infection, and they underscore the importance of the often ignored low-affinity ligand-receptor interactions.

Original languageEnglish
Pages (from-to)5948-5963
Number of pages16
JournalEMBO Journal
Volume17
Issue number20
DOIs
Publication statusPublished - Oct 15 1998

Keywords

  • DNA virus
  • Growth factor
  • Oncogene
  • Signal transduction
  • Tyrosine kinase

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Fingerprint Dive into the research topics of 'Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network'. Together they form a unique fingerprint.

  • Cite this

    Tzahar, E., Moyer, J. D., Waterman, H., Barbacci, E. G., Bao, J., Levkowitz, G., Shelly, M., Strano, S., Pinkas-Kramarski, R., Pierce, J. H., Andrews, G. C., & Yarden, Y. (1998). Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network. EMBO Journal, 17(20), 5948-5963. https://doi.org/10.1093/emboj/17.20.5948