Article
- The EMBO Journal (1998) 17, 5948 - 5963
- doi:10.1093/emboj/17.20.5948
Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network
Eldad Tzahar1, James D. Moyer2, Hadassa Waterman1, Elsa G. Barbacci2, Jing Bao1, Gil Levkowitz1, Maya Shelly1, Sabrina Strano1, Ronit Pinkas-Kramarski1, Jacalyn H. Pierce3, Glenn C. Andrews2 and Yosef Yarden1
- Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
- Pfizer Central Research, Groton, CT 06340, USA
- National Cancer Institute, Bethesda, MD 20892, USA
Correspondence to:
Yosef Yarden, E-mail: liyarden@weizmann.weizmann.ac.il
Received 26 February 1998; Accepted 25 August 1998; Revised 17 August 1998
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.
Keywords:
- DNA virus,
- growth factor,
- oncogene,
- signal transduction,
- tyrosine kinase
