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Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network
Author(s) -
Tzahar Eldad,
Moyer James D.,
Waterman Hadassa,
Barbacci Elsa G.,
Bao Jing,
Levkowitz Gil,
Shelly Maya,
Strano Sabrina,
PinkasKramarski Ronit,
Pierce Jacalyn H.,
Andrews Glenn C.,
Yarden Yosef
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.20.5948
Subject(s) - library science , biology , computer science
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.

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