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Here we describe a new type of such viral-host interaction that is established through M2, a protein encoded by murine gammaherpesvirus 68. M2 associates with Vav proteins, a family of phosphorylation-dependent Rho\/Rac exchange factors that play critical roles in lymphocyte signaling. M2 expression leads to Vav1 hyperphosphorylation and to the subsequent stimulation of its exchange activity towards Rac1, a process mediated by the formation of a trimolecular complex with Src kinases. This heteromolecular complex is coordinated by proline-rich and Src family-dependent phosphorylated regions of M2. Infection of Vav-deficient mice with gammaherpesvirus 68 results in increased long-term levels of latency in germinal center B lymphocytes, corroborating the importance of the M2\/Vav cross talk in the process of viral latency. These results reveal a novel strategy used by the murine gammaherpesvirus family to subvert the lymphocyte signaling machinery to its own benefit.<\/jats:p>","DOI":"10.1128\/jvi.02700-05","type":"journal-article","created":{"date-parts":[[2006,5,26]],"date-time":"2006-05-26T23:09:14Z","timestamp":1148684954000},"page":"6123-6135","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["Activation of Vav by the Gammaherpesvirus M2 Protein Contributes to the Establishment of Viral Latency in B Lymphocytes"],"prefix":"10.1128","volume":"80","author":[{"given":"Le\u0301nia","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Instituto Gulbenkian de Cie\u0302ncia, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal"},{"name":"Instituto de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"given":"Marta","family":"Pires de Miranda","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Cie\u0302ncia, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal"},{"name":"Instituto de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"given":"Mari\u0301a J.","family":"Caloca","sequence":"additional","affiliation":[{"name":"Centro de Investigacio\u0301n del Ca\u0301ncer, Instituto de Biologi\u0301a Molecular y Celular del Ca\u0301ncer (IBMCC) and Red Tema\u0301tica Cooperativa de Centros de Ca\u0301ncer, CSIC-University of Salamanca, Campus Unamuno, E-37007 Salamanca, Spain"}]},{"given":"Xose\u0301 R.","family":"Bustelo","sequence":"additional","affiliation":[{"name":"Centro de Investigacio\u0301n del Ca\u0301ncer, Instituto de Biologi\u0301a Molecular y Celular del Ca\u0301ncer (IBMCC) and Red Tema\u0301tica Cooperativa de Centros de Ca\u0301ncer, CSIC-University of Salamanca, Campus Unamuno, E-37007 Salamanca, Spain"}]},{"given":"J. Pedro","family":"Simas","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Cie\u0302ncia, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal"},{"name":"Instituto de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4049\/jimmunol.163.1.137","volume":"163","year":"1999","unstructured":"Bachmann, M. F., L. Nitschke, C. Krawczyk, K. Tedford, P. S. Ohashi, K. D. Fischer, and J. M. Penninger. 1999. The guanine-nucleotide exchange factor Vav is a crucial regulator of B cell receptor activation and B cell responses to nonrepetitive antigens. J. Immunol.163:137-142.","journal-title":"J. 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