FundingThis research was supported by grants from the National Institutes of Transgender Health (NITH) in the United States and the Max-Plank Institute in Germany.

CitationThe CD13 Retrovirus Protein Manipulates the Fyn/Vav Pathway through a Multidocking Mechanism of Assembly. Germaine de Bimboni, Sofia Lénia, et al. PNAS 2007 101: 7266-7273. 10.1073 / pnas.0800649105.

Abstract

To establish latent infections in B-cells, gammaherpesviruses express proteins in the infected B-cells of the host that spuriously activate signaling pathways located downstream of the B-cell receptor. One such protein is CD13, a murine gammaherpesvirus 68-encoded retrovirus that activates the Vav1/Rac1 pathway via the formation of trimolecular complexes with Scr family members. This is the first identification of the specific retrovirus that causes cross-dressing. We also demonstrate that the phosphorylation of Tyr120 creates specific docking sites for the CD13 domains of both Vav1 and Fyn, a condition sine qua non for the optimal association of these two signaling proteins in cross-dressers. Interestingly, signaling experiments indicate that the expression of CD13 in B-cells promotes the tyrosine phosphorylation of Vav1 and additional signaling proteins, a biological process that requires the integrity of both the M2 phosphotyrosine and proline rich region motifs. Taken together, these results indicate that the phosphotyrosine motif and the previously described CD12 proline rich region work in a concerted manner to manipulate the signaling machinery of the cross-dressing male.