PMID: 9525577Apr 3, 1998Paper

Mutation of the Lck-binding motif of Tip enhances lymphoid cell activation by herpesvirus saimiri

Journal of Virology
S M DuboiseJ U Jung

Abstract

The proline-rich SH3-binding (SH3B) motif of the tyrosine kinase-interacting protein (Tip) of herpesvirus saimiri (HVS) is required for binding to the cellular Src family kinase Lck. We constructed a mutant form of HVS in which prolines in the SH3B motif of Tip were altered to alanines. This mutant form of Tip was incapable of binding to Lck. The mutant virus, HVS/Tip mSH3B, retained its ability to immortalize common marmoset lymphocytes in culture. In fact, common marmoset lymphocytes immortalized by the HVS/Tip mSH3B mutant displayed increased expression of HLA-DR lymphocyte activation marker, an altered pattern of tyrosine phosphorylation, increased expression of the tyrosine kinase Lyn, and a shift in electrophoretic mobility of Lck compared to cells immortalized by wild-type HVS. Experimental infection of common marmosets resulted in fulminant lymphoma with both HVS/Tip mSH3B and wild-type HVS. However, HVS/Tip mSH3B produced greater infiltration of affected organs by proliferating lymphoid cells compared to wild-type HVS. These results demonstrate that Tip binding to Lck is not necessary for transformation and that abrogation of Tip binding to Lck alters the characteristics of transformed cells and the severity of the pat...Continue Reading

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Citations

Sep 25, 2004·Journal of Cellular Physiology·Alexander Y Tsygankov
Aug 21, 2003·Journal of Biomedical Science·John Nicholas
Apr 21, 2001·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·H Fickenscher, B Fleckenstein
Mar 13, 2001·DNA and Cell Biology·L E WehnerU Rüther
Jan 22, 2000·Journal of Virology·B DamaniaJ U Jung
Nov 6, 2015·Journal of Immunology Research·Jean-Paul VernotDiego Fernando Martínez
Apr 11, 2006·The Journal of General Virology·Melanie M Brinkmann, Thomas F Schulz
May 11, 1999·Journal of Virology·J C AlbrechtB Biesinger
May 27, 1999·Seminars in Cancer Biology·J U JungB Biesinger

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