{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:50:23Z","timestamp":1791571823164,"version":"4.3.4"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"22","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010434","name":"\"la Caixa\" Foundation","doi-asserted-by":"publisher","award":["HR20\u201000164"],"award-info":[{"award-number":["HR20\u201000164"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["CSI252P18"],"award-info":[{"award-number":["CSI252P18"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["CLC\u20102017\u201001"],"award-info":[{"award-number":["CLC\u20102017\u201001"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["CSI145P20"],"award-info":[{"award-number":["CSI145P20"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"MEC|Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/01724"],"award-info":[{"award-number":["PI20\/01724"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"MEC|Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["BES\u20102013\u2010063573"],"award-info":[{"award-number":["BES\u20102013\u2010063573"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["FPU13\/02923"],"award-info":[{"award-number":["FPU13\/02923"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"MEC|Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["RTI2018\u2010096481\u2010B\u2010100"],"award-info":[{"award-number":["RTI2018\u2010096481\u2010B\u2010100"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["GC16173472GARC"],"award-info":[{"award-number":["GC16173472GARC"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2021,11,15]]},"DOI":"10.15252\/embj.2021108125","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T01:51:20Z","timestamp":1633744280000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cancer\u2010associated mutations in VAV1 trigger variegated signaling outputs and T\u2010cell lymphomagenesis"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-0187","authenticated-orcid":false,"given":"Javier","family":"Robles\u2010Valero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1757-6650","authenticated-orcid":false,"given":"Luc\u00eda","family":"Fern\u00e1ndez\u2010Nevado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4717-9338","authenticated-orcid":false,"given":"L Francisco","family":"Lorenzo\u2010Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-1205","authenticated-orcid":false,"given":"Myriam","family":"Cuadrado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5130-2143","authenticated-orcid":false,"given":"Isabel","family":"Fern\u00e1ndez\u2010Pisonero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5369-2969","authenticated-orcid":false,"given":"Sonia","family":"Rodr\u00edguez\u2010Fdez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2317-1094","authenticated-orcid":false,"given":"Elsa N","family":"Astorga\u2010Sim\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-2775","authenticated-orcid":false,"given":"Antonio","family":"Abad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1325-896X","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Caloto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9398-6072","authenticated-orcid":false,"given":"Xos\u00e9 R","family":"Bustelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"BFEMBJ2021108125_CR1","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1073\/pnas.1608839114","volume":"114","author":"F Abate","year":"2017","unstructured":"Abate F, da Silva\u2010Almeida AC, Zairis S, Robles\u2010Valero J, Couronne L, Khiabanian H, Quinn SA, Kim M\u2010Y, Laginestra MA, Kim C et\u00a0al (2017) Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T\u2010cell lymphomas. Proc Natl Acad Sci U S A 114: 764\u2013769","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFEMBJ2021108125_CR2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0092-8674(00)00085-4","volume":"102","author":"B Aghazadeh","year":"2000","unstructured":"Aghazadeh B, Lowry WE, Huang XY, Rosen MK (2000) Structural basis for relief of autoinhibition of the Dbl homology domain of proto\u2010oncogene Vav by tyrosine phosphorylation. Cell 102: 625\u2013633","journal-title":"Cell"},{"key":"BFEMBJ2021108125_CR3","doi-asserted-by":"crossref","first-page":"ra35","DOI":"10.1126\/scisignal.2004993","volume":"7","author":"M Barreira","year":"2014","unstructured":"Barreira M, Fabbiano S, Couceiro JR, Torreira E, Mart\u00ednez\u2010Torrecuadrada JL, Montoya G, Llorca O, Bustelo XR (2014) The C\u2010terminal SH3 domain contributes to the intramolecular inhibition of Vav family proteins. Sci Signal 7: ra35","journal-title":"Sci Signal"},{"key":"BFEMBJ2021108125_CR4","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cellsig.2018.01.026","volume":"45","author":"M Barreira","year":"2018","unstructured":"Barreira M, Rodriguez\u2010Fdez S, Bustelo XR (2018) New insights into the Vav1 activation cycle in lymphocytes. Cell Signal 45: 132\u2013144","journal-title":"Cell Signal"},{"key":"BFEMBJ2021108125_CR5","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1182\/blood-2016-03-707141","volume":"128","author":"RL Boddicker","year":"2016","unstructured":"Boddicker RL, Razidlo GL, Dasari S, Zeng YU, Hu G, Knudson RA, Greipp PT, Davila JI, Johnson SH, Porcher JC et\u00a0al (2016) Integrated mate\u2010pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T\u2010cell lymphoma. Blood 128: 1234\u20131245","journal-title":"Blood"},{"key":"BFEMBJ2021108125_CR6","doi-asserted-by":"crossref","DOI":"10.4161\/21541248.2014.973757","volume":"5","author":"XR Bustelo","year":"2014","unstructured":"Bustelo XR (2014) Vav family exchange factors: an integrated regulatory and functional view. Small GTPases 5: e973757","journal-title":"Small GTPases"},{"key":"BFEMBJ2021108125_CR7","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1126\/science.256.5060.1196","volume":"256","author":"XR Bustelo","year":"1992","unstructured":"Bustelo XR, Barbacid M (1992) Tyrosine phosphorylation of the vav proto\u2010oncogene product in activated B cells. Science 256: 1196\u20131199","journal-title":"Science"},{"key":"BFEMBJ2021108125_CR8","first-page":"1","volume-title":"Encyclopedia of signaling molecules","author":"XR Bustelo","year":"2016","unstructured":"Bustelo XR, Dosil M (2016) The Vav family. In: Encyclopedia of signaling molecules, Choi S (ed.), pp. 1\u201315. New York, NY: Springer"},{"key":"BFEMBJ2021108125_CR9","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/356068a0","volume":"356","author":"XR Bustelo","year":"1992","unstructured":"Bustelo XR, Ledbetter JA, Barbacid M (1992) Product of vav proto\u2010oncogene defines a new class of tyrosine protein kinase substrates. Nature 356: 68\u201371","journal-title":"Nature"},{"key":"BFEMBJ2021108125_CR10","first-page":"297","volume":"4","author":"XR Bustelo","year":"1993","unstructured":"Bustelo XR, Rubin SD, Suen KL, Carrasco D, Barbacid M (1993) Developmental expression of the vav protooncogene. Cell Growth Differ 4: 297\u2013308","journal-title":"Cell Growth Differ"},{"key":"BFEMBJ2021108125_CR11","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1128\/MCB.15.3.1324","volume":"15","author":"XR Bustelo","year":"1995","unstructured":"Bustelo XR, Suen KL, Michael WM, Dreyfuss G, Barbacid M (1995) Association of the vav proto\u2010oncogene product with poly(rC)\u2010specific RNA\u2010binding proteins. Mol Cell Biol 15: 1324\u20131332","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2021108125_CR12","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/ng.3564","volume":"48","author":"JD Campbell","year":"2016","unstructured":"Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, Shukla SA, Guo G, Brooks AN, Murray BA et\u00a0al (2016) Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet 48: 607\u2013616","journal-title":"Nat Genet"},{"key":"BFEMBJ2021108125_CR13","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1038\/s41375-020-0990-y","volume":"34","author":"S Chiba","year":"2020","unstructured":"Chiba S, Sakata\u2010Yanagimoto M (2020) Advances in understanding of angioimmunoblastic T\u2010cell lymphoma. Leukemia 34: 2592\u20132606","journal-title":"Leukemia"},{"key":"BFEMBJ2021108125_CR14","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.jmb.2008.05.024","volume":"380","author":"JE Chrencik","year":"2008","unstructured":"Chrencik JE, Brooun A, Zhang H, Mathews II, Hura GL, Foster SA, Perry JJP, Streiff M, Ramage P, Widmer H et\u00a0al (2008) Structural basis of guanine nucleotide exchange mediated by the T\u2010cell essential Vav1. J Mol Biol 380: 828\u2013843","journal-title":"J Mol Biol"},{"key":"BFEMBJ2021108125_CR15","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/357695a0","volume":"357","author":"NA Clipstone","year":"1992","unstructured":"Clipstone NA, Crabtree GR (1992) Identification of calcineurin as a key signalling enzyme in T\u2010lymphocyte activation. Nature 357: 695\u2013697","journal-title":"Nature"},{"key":"BFEMBJ2021108125_CR16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ccell.2018.01.001","volume":"33","author":"JR Cortes","year":"2018","unstructured":"Cortes JR, Ambesi\u2010Impiombato A, Couronne L, Quinn SA, Kim CS, da Silva Almeida AC, West Z, Belver L, Martin MS, Scourzic L et\u00a0al (2018) RHOAG17V Induces T follicular helper cell specification and promotes lymphomagenesis. Cancer Cell 33: 259\u2013273.e257","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021108125_CR17","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.yexcr.2005.04.035","volume":"308","author":"JR Couceiro","year":"2005","unstructured":"Couceiro JR, Martin\u2010Bermudo MD, Bustelo XR (2005) Phylogenetic conservation of the regulatory and functional properties of the Vav oncoprotein family. Exp Cell Res 308: 364\u2013380","journal-title":"Exp Cell Res"},{"key":"BFEMBJ2021108125_CR18","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.ccell.2015.03.006","volume":"27","author":"R Crescenzo","year":"2015","unstructured":"Crescenzo R, Abate F, Lasorsa E, Tabbo\u2019 F, Gaudiano M, Chiesa N, Di Giacomo F, Spaccarotella E, Barbarossa L, Ercole E et\u00a0al (2015) Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell 27: 516\u2013532","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021108125_CR19","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/385169a0","volume":"385","author":"P Crespo","year":"1997","unstructured":"Crespo P, Schuebel KE, Ostrom AA, Gutkind JS, Bustelo XR (1997) Phosphotyrosine\u2010dependent activation of Rac\u20101 GDP\/GTP exchange by the vav proto\u2010oncogene product. Nature 385: 169\u2013172","journal-title":"Nature"},{"key":"BFEMBJ2021108125_CR20","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1182\/blood-2006-10-055145","volume":"109","author":"L de Leval","year":"2007","unstructured":"de Leval L, Rickman DS, Thielen C, Reynies AD, Huang Y\u2010L, Delsol G, Lamant L, Leroy K, Bri\u00e8re J, Molina T et\u00a0al (2007) The gene expression profile of nodal peripheral T\u2010cell lymphoma demonstrates a molecular link between angioimmunoblastic T\u2010cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood 109: 4952\u20134963","journal-title":"Blood"},{"key":"BFEMBJ2021108125_CR21","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41568-020-0247-0","volume":"20","author":"D Fiore","year":"2020","unstructured":"Fiore D, Cappelli LV, Broccoli A, Zinzani PL, Chan WC, Inghirami G (2020) Peripheral T cell lymphomas: from the bench to the clinic. Nat Rev Cancer 20: 323\u2013342","journal-title":"Nat Rev Cancer"},{"key":"BFEMBJ2021108125_CR22","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1084\/jem.20030874","volume":"198","author":"K Fujikawa","year":"2003","unstructured":"Fujikawa K, Miletic AV, Alt FW, Faccio R, Brown T, Hoog J, Fredericks J, Nishi S, Mildiner S, Moores SL et\u00a0al (2003) Vav1\/2\/3\u2010null mice define an essential role for Vav family proteins in lymphocyte development and activation but a differential requirement in MAPK signaling in T and B cells. J Exp Med 198: 1595\u20131608","journal-title":"J Exp Med"},{"key":"BFEMBJ2021108125_CR23","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1182\/blood.2020006513","volume":"136","author":"K Fukumoto","year":"2020","unstructured":"Fukumoto K, Sakata\u2010Yanagimoto M, Fujisawa M, Sakamoto T, Miyoshi H, Suehara Y, Nguyen TB, Suma S, Yanagimoto S, Shiraishi Y et\u00a0al (2020) VAV1 mutations contribute to development of T\u2010cell neoplasms in mice. Blood 136: 3018\u20133032","journal-title":"Blood"},{"key":"BFEMBJ2021108125_CR24","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ccell.2015.09.001","volume":"28","author":"M Gallardo","year":"2015","unstructured":"Gallardo M, Lee H, Zhang X, Bueso\u2010Ramos C, Pageon L, McArthur M, Multani A, Nazha A, Manshouri T, Parker\u2010Thornburg J et\u00a0al (2015) hnRNP K is a haploinsufficient tumor suppressor that regulates proliferation and differentiation programs in hematologic malignancies. Cancer Cell 28: 486\u2013499","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021108125_CR25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/ni1168","volume":"6","author":"TS Gomez","year":"2005","unstructured":"Gomez TS, Hamann MJ, McCarney S, Savoy DN, Lubking CM, Heldebrant MP, Labno CM, McKean DJ, McNiven MA, Burkhardt JK et\u00a0al (2005) Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse. Nat Immunol 6: 261\u2013270","journal-title":"Nat Immunol"},{"key":"BFEMBJ2021108125_CR26","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/(SICI)1521-4141(199902)29:02<477::AID-IMMU477>3.0.CO;2-V","volume":"29","author":"A Gulbranson\u2010Judge","year":"1999","unstructured":"Gulbranson\u2010Judge A, Tybulewicz VL, Walters AE, Toellner KM, MacLennan IC, Turner M (1999) Defective immunoglobulin class switching in Vav\u2010deficient mice is attributable to compromised T cell help. Eur J Immunol 29: 477\u2013487","journal-title":"Eur J Immunol"},{"key":"BFEMBJ2021108125_CR27","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1093\/nar\/gkt1323","volume":"42","author":"M Gustems","year":"2014","unstructured":"Gustems M, Woellmer A, Rothbauer U, Eck SH, Wieland T, Lutter D, Hammerschmidt W (2014) c\u2010Jun\/c\u2010Fos heterodimers regulate cellular genes via a newly identified class of methylated DNA sequence motifs. Nucleic Acids Res 42: 3059\u20133072","journal-title":"Nucleic Acids Res"},{"key":"BFEMBJ2021108125_CR28","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1084\/jem.20141380","volume":"212","author":"K Hatzi","year":"2015","unstructured":"Hatzi K, Nance JP, Kroenke MA, Bothwell M, Haddad EK, Melnick A, Crotty S (2015) BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms. J Exp Med 212: 539\u2013553","journal-title":"J Exp Med"},{"key":"BFEMBJ2021108125_CR29","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1182\/blood-2018-09-872549","volume":"133","author":"TB Heavican","year":"2019","unstructured":"Heavican TB, Bouska A, Yu J, Lone W, Amador C, Gong Q, Zhang W, Li Y, Dave BJ, Nairism\u00e4gi M\u2010L et\u00a0al (2019) Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T\u2010cell lymphoma. Blood 133: 1664\u20131676","journal-title":"Blood"},{"key":"BFEMBJ2021108125_CR30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029939","volume":"7","author":"L Ilan","year":"2012","unstructured":"Ilan L, Katzav S (2012) Human Vav1 expression in hematopoietic and cancer cell lines is regulated by c\u2010Myb and by CpG methylation. PLoS One 7: e29939","journal-title":"PLoS One"},{"key":"BFEMBJ2021108125_CR31","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1016\/j.ajpath.2015.07.021","volume":"185","author":"S Jain","year":"2015","unstructured":"Jain S, Chen J, Nicolae A, Wang H, Shin D\u2010M, Adkins EB, Sproule TJ, Leeth CM, Sakai T, Kovalchuk AL et\u00a0al (2015) IL\u201021\u2010driven neoplasms in SJL mice mimic some key features of human angioimmunoblastic T\u2010cell lymphoma. Am J Pathol 185: 3102\u20133114","journal-title":"Am J Pathol"},{"key":"BFEMBJ2021108125_CR32","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/ng.3415","volume":"47","author":"K Kataoka","year":"2015","unstructured":"Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga J\u2010I, Totoki Y, Chiba K, Sato\u2010Otsubo A, Nagae G et\u00a0al (2015) Integrated molecular analysis of adult T cell leukemia\/lymphoma. Nat Genet 47: 1304\u20131315","journal-title":"Nat Genet"},{"key":"BFEMBJ2021108125_CR33","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1002\/j.1460-2075.1989.tb08354.x","volume":"8","author":"S Katzav","year":"1989","unstructured":"Katzav S, Martin\u2010Zanca D, Barbacid M (1989) Vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells. EMBO J 8: 2283\u20132290","journal-title":"EMBO J"},{"key":"BFEMBJ2021108125_CR34","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cell.2009.03.045","volume":"137","author":"R Kopan","year":"2009","unstructured":"Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137: 216\u2013233","journal-title":"Cell"},{"key":"BFEMBJ2021108125_CR35","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1074\/jbc.275.3.2185","volume":"275","author":"MR Kuhne","year":"2000","unstructured":"Kuhne MR, Ku G, Weiss A (2000) A guanine nucleotide exchange factor\u2010independent function of Vav1 in transcriptional activation. J Biol Chem 275: 2185\u20132190","journal-title":"J Biol Chem"},{"key":"BFEMBJ2021108125_CR36","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1084\/jem.20081561","volume":"205","author":"X Li","year":"2008","unstructured":"Li X, Gounari F, Protopopov A, Khazaie K, von Boehmer H (2008) Oncogenesis of T\u2010ALL and nonmalignant consequences of overexpressing intracellular NOTCH1. J Exp Med 205: 2851\u20132861","journal-title":"J Exp Med"},{"key":"BFEMBJ2021108125_CR37","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1128\/MCB.20.5.1678-1691.2000","volume":"20","author":"M Lopez\u2010Lago","year":"2000","unstructured":"Lopez\u2010Lago M, Lee H, Cruz C, Movilla N, Bustelo XR (2000) Tyrosine phosphorylation mediates both activation and downmodulation of the biological activity of Vav. Mol Cell Biol 20: 1678\u20131691","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2021108125_CR38","doi-asserted-by":"crossref","first-page":"4788","DOI":"10.1038\/s41467-020-18524-3","volume":"11","author":"LF Lorenzo\u2010Mart\u00edn","year":"2020","unstructured":"Lorenzo\u2010Mart\u00edn LF, Fern\u00e1ndez\u2010Parejo N, Menacho\u2010M\u00e1rquez M, Rodr\u00edguez\u2010Fdez S, Robles\u2010Valero J, Zumalave S, Fabbiano S, Pascual G, Garc\u00eda\u2010Pedrero JM, Abad A et\u00a0al (2020) VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma. Nat Commun 11: 4788","journal-title":"Nat Commun"},{"key":"BFEMBJ2021108125_CR39","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","volume":"169","author":"BD Manning","year":"2017","unstructured":"Manning BD, Toker A (2017) AKT\/PKB signaling: navigating the network. Cell 169: 381\u2013405","journal-title":"Cell"},{"key":"BFEMBJ2021108125_CR40","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.4049\/jimmunol.1501841","volume":"196","author":"GJ Martinez","year":"2016","unstructured":"Martinez GJ, Hu JK, Pereira RM, Crampton JS, Togher S, Bild N, Crotty S, Rao A (2016) Cutting edge: NFAT transcription factors promote the generation of follicular helper T cells in response to acute viral infection. J Immunol 196: 2015\u20132019","journal-title":"J Immunol"},{"key":"BFEMBJ2021108125_CR41","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/ajh.25450","volume":"94","author":"F Maura","year":"2019","unstructured":"Maura F, Agnelli L, Leongamornlert D, Bolli N, Chan WC, Dodero A, Carniti C, Heavican TB, Pellegrinelli A, Pruneri G et\u00a0al (2019) Integration of transcriptional and mutational data simplifies the stratification of peripheral T\u2010cell lymphoma. Am J Hematol 94: 628\u2013634","journal-title":"Am J Hematol"},{"key":"BFEMBJ2021108125_CR42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1001615","volume":"11","author":"M Menacho\u2010Marquez","year":"2013","unstructured":"Menacho\u2010Marquez M, Garcia\u2010Escudero R, Ojeda V, Abad A, Delgado P, Costa C, Ruiz S, Alarcon B, Paramio JM, Bustelo XR (2013) The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops. PLoS Biol 11: e1001615","journal-title":"PLoS Biol"},{"key":"BFEMBJ2021108125_CR43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41389-020-00259-x","volume":"9","author":"R Mhaidly","year":"2020","unstructured":"Mhaidly R, Krug A, Gaulard P, Lemonnier F, Ricci JE, Verhoeyen E (2020) New preclinical models for angioimmunoblastic T\u2010cell lymphoma: filling the GAP. Oncogenesis 9: 73","journal-title":"Oncogenesis"},{"key":"BFEMBJ2021108125_CR44","doi-asserted-by":"crossref","first-page":"735","DOI":"10.3389\/fimmu.2020.00735","volume":"11","author":"A Mitra","year":"2020","unstructured":"Mitra A, Shanthalingam S, Sherman HL, Singh K, Canakci M, Torres JA, Lawlor R, Ran Y, Golde TE, Miele L et\u00a0al (2020) CD28 signaling drives notch ligand expression on CD4 T cells. Front Immunol 11: 735","journal-title":"Front Immunol"},{"key":"BFEMBJ2021108125_CR45","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s43018-020-00161-w","volume":"2","author":"CS Moon","year":"2021","unstructured":"Moon CS, Reglero C, Cortes JR, Quinn SA, Alvarez S, Zhao J, Lin WW, Cooke AJ, Abate F, Soderquist CR et\u00a0al (2021) FYN\u2010TRAF3IP2 induces NF\u2010\u03baB signaling\u2010driven peripheral T cell lymphoma. Nat Cancer 2: 98\u2013113","journal-title":"Nat Cancer"},{"key":"BFEMBJ2021108125_CR46","doi-asserted-by":"crossref","first-page":"7870","DOI":"10.1128\/MCB.19.11.7870","volume":"19","author":"N Movilla","year":"1999","unstructured":"Movilla N, Bustelo XR (1999) Biological and regulatory properties of Vav\u20103, a new member of the Vav family of oncoproteins. Mol Cell Biol 19: 7870\u20137885","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2021108125_CR47","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nri2818","volume":"10","author":"MR Muller","year":"2010","unstructured":"Muller MR, Rao A (2010) NFAT, immunity and cancer: a transcription factor comes of age. Nat Rev Immunol 10: 645\u2013656","journal-title":"Nat Rev Immunol"},{"key":"BFEMBJ2021108125_CR48","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.4049\/jimmunol.171.6.3019","volume":"171","author":"T Palaga","year":"2003","unstructured":"Palaga T, Miele L, Golde TE, Osborne BA (2003) TCR\u2010mediated Notch signaling regulates proliferation and IFN\u2010gamma production in peripheral T cells. J Immunol 171: 3019\u20133024","journal-title":"J Immunol"},{"key":"BFEMBJ2021108125_CR49","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1182\/blood-2017-02-768234","volume":"130","author":"J Park","year":"2017","unstructured":"Park J, Yang J, Wenzel AT, Ramachandran A, Lee WJ, Daniels JC, Kim J, Martinez\u2010Escala E, Amankulor N, Pro B et\u00a0al (2017) Genomic analysis of 220 CTCLs identifies a novel recurrent gain\u2010of\u2010function alteration in RLTPR (p. Q575E). Blood 130: 1430\u20131440","journal-title":"Blood"},{"key":"BFEMBJ2021108125_CR50","doi-asserted-by":"crossref","first-page":"10703","DOI":"10.1158\/0008-5472.CAN-07-1708","volume":"67","author":"PP Piccaluga","year":"2007","unstructured":"Piccaluga PP, Agostinelli C, Califano A, Carbone A, Fantoni L, Ferrari S, Gazzola A, Gloghini A, Righi S, Rossi M et\u00a0al (2007) Gene expression analysis of angioimmunoblastic lymphoma indicates derivation from T follicular helper cells and vascular endothelial growth factor deregulation. Cancer Res 67: 10703\u201310710","journal-title":"Cancer Res"},{"key":"BFEMBJ2021108125_CR51","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/embor.2008.80","volume":"9","author":"J Rapley","year":"2008","unstructured":"Rapley J, Tybulewicz VL, Rittinger K (2008) Crucial structural role for the PH and C1 domains of the Vav1 exchange factor. EMBO Rep 9: 655\u2013661","journal-title":"EMBO Rep"},{"key":"BFEMBJ2021108125_CR52","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.ccell.2017.10.004","volume":"32","author":"J Robles\u2010Valero","year":"2017","unstructured":"Robles\u2010Valero J, Lorenzo\u2010Martin LF, Menacho\u2010Marquez M, Fernandez\u2010Pisonero I, Abad A, Camos M, Toribio ML, Espinosa L, Bigas A, Bustelo XR (2017) A paradoxical tumor\u2010suppressor role for the Rac1 exchange factor Vav1 in T cell acute lymphoblastic leukemia. Cancer Cell 32: 608\u2013623.e609","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021108125_CR53","volume":"8","author":"S Rodriguez\u2010Fdez","year":"2019","unstructured":"Rodriguez\u2010Fdez S, Bustelo XR (2019) The Vav GEF family: an evolutionary and functional perspective. Cells 8: E465","journal-title":"Cells"},{"key":"BFEMBJ2021108125_CR54","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3390\/cells9030609","volume":"9","author":"S Rodr\u00edguez\u2010Fdez","year":"2020","unstructured":"Rodr\u00edguez\u2010Fdez S, Fern\u00e1ndez\u2010Nevado L, Lorenzo\u2010Mart\u00edn LF, Bustelo XR (2020) Lysine acetylation reshapes the downstream signaling landscape of Vav1 in lymphocytes. Cells 9: 609","journal-title":"Cells"},{"key":"BFEMBJ2021108125_CR55","doi-asserted-by":"crossref","first-page":"6608","DOI":"10.1093\/emboj\/17.22.6608","volume":"17","author":"KE Schuebel","year":"1998","unstructured":"Schuebel KE, Movilla N, Rosa JL, Bustelo XR (1998) Phosphorylation\u2010dependent and constitutive activation of Rho proteins by wild\u2010type and oncogenic Vav\u20102. EMBO J 17: 6608\u20136621","journal-title":"EMBO J"},{"key":"BFEMBJ2021108125_CR56","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-019-1324-y","volume":"571","author":"AC Scott","year":"2019","unstructured":"Scott AC, D\u00fcndar F, Zumbo P, Chandran SS, Klebanoff CA, Shakiba M, Trivedi P, Menocal L, Appleby H, Camara S et\u00a0al (2019) TOX is a critical regulator of tumour\u2010specific T cell differentiation. Nature 571: 270\u2013274","journal-title":"Nature"},{"key":"BFEMBJ2021108125_CR57","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1471-2199-5-13","volume":"5","author":"A Selvaraj","year":"2004","unstructured":"Selvaraj A, Prywes R (2004) Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent. BMC Mol Biol 5: 13","journal-title":"BMC Mol Biol"},{"key":"BFEMBJ2021108125_CR58","doi-asserted-by":"crossref","first-page":"997","DOI":"10.4049\/jimmunol.1700070","volume":"200","author":"MP Steinbuck","year":"2018","unstructured":"Steinbuck MP, Arakcheeva K, Winandy S (2018) Novel TCR\u2010mediated mechanisms of notch activation and signaling. J Immunol 200: 997\u20131007","journal-title":"J Immunol"},{"key":"BFEMBJ2021108125_CR59","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1182\/blood-2004-10-4074","volume":"106","author":"Y Tanaka","year":"2005","unstructured":"Tanaka Y, So T, Lebedeva S, Croft M, Altman A (2005) Impaired IL\u20104 and c\u2010Maf expression and enhanced Th1\u2010cell development in Vav1\u2010deficient mice. Blood 106: 1286\u20131295","journal-title":"Blood"},{"key":"BFEMBJ2021108125_CR60","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1182\/blood-2016-02-698977","volume":"128","author":"D Vallois","year":"2016","unstructured":"Vallois D, Dobay MPD, Morin RD, Lemonnier F, Missiaglia E, Juilland M, Iwaszkiewicz J, Fataccioli V, Bisig B, Roberti A et\u00a0al (2016) Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T\u2010cell\u2010derived lymphomas. Blood 128: 1490\u20131502","journal-title":"Blood"},{"key":"BFEMBJ2021108125_CR61","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1182\/blood-2014-06-582700","volume":"124","author":"JS Weinstein","year":"2014","unstructured":"Weinstein JS, Lezon\u2010Geyda K, Maksimova Y, Craft S, Zhang Y, Su M, Schulz VP, Craft J, Gallagher PG (2014) Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes. Blood 124: 3719\u20133729","journal-title":"Blood"},{"key":"BFEMBJ2021108125_CR62","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1128\/MCB.15.8.4337","volume":"15","author":"J Wu","year":"1995","unstructured":"Wu J, Katzav S, Weiss A (1995) A functional T\u2010cell receptor signaling pathway is required for p95vav activity. Mol Cell Biol 15: 4337\u20134346","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2021108125_CR63","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.immuni.2019.10.006","volume":"51","author":"W Xu","year":"2019","unstructured":"Xu W, Zhao X, Wang X, Feng H, Gou M, Jin W, Wang X, Liu X, Dong C (2019) The transcription factor Tox2 drives T follicular helper cell development via regulating chromatin accessibility. Immunity 51: 826\u2013839.e825","journal-title":"Immunity"},{"key":"BFEMBJ2021108125_CR64","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/ng.2916","volume":"46","author":"HY Yoo","year":"2014","unstructured":"Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, Kim SC, Lee B, Rho K, Lee J\u2010E et\u00a0al (2014) A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet 46: 371\u2013375","journal-title":"Nat Genet"},{"key":"BFEMBJ2021108125_CR65","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.cell.2009.12.033","volume":"140","author":"B Yu","year":"2010","unstructured":"Yu B, Martins IR, Li P, Amarasinghe GK, Umetani J, Fernandez\u2010Zapico ME, Billadeau DD, Machius M, Tomchick DR, Rosen MK (2010) Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1. Cell 140: 246\u2013256","journal-title":"Cell"},{"key":"BFEMBJ2021108125_CR66","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1172\/JCI92026","volume":"127","author":"S Zang","year":"2017","unstructured":"Zang S, Li J, Yang H, Zeng H, Han W, Zhang J, Lee M, Moczygemba M, Isgandarova S, Yang Y et\u00a0al (2017) Mutations in 5\u2010methylcytosine oxidase TET2 and RhoA cooperatively disrupt T cell homeostasis. J Clin Invest 127: 2998\u20133012","journal-title":"J Clin Invest"},{"key":"BFEMBJ2021108125_CR67","doi-asserted-by":"crossref","first-page":"197","DOI":"10.12659\/MSM.896545","volume":"22","author":"Z Zhang","year":"2016","unstructured":"Zhang Z, Chen C, Guo W, Zheng S, Sun Z, Geng X (2016) DNM3 attenuates hepatocellular carcinoma growth by activating P53. Med Sci Monit 22: 197\u2013205","journal-title":"Med Sci Monit"},{"key":"BFEMBJ2021108125_CR68","doi-asserted-by":"crossref","first-page":"45377","DOI":"10.1074\/jbc.M208039200","volume":"277","author":"JL Zugaza","year":"2002","unstructured":"Zugaza JL, Lopez\u2010Lago MA, Caloca MJ, Dosil M, Movilla N, Bustelo XR (2002) Structural determinants for the biological activity of Vav proteins. J Biol Chem 277: 45377\u201345392","journal-title":"J Biol Chem"}],"container-title":["The EMBO Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embj.2021108125.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/embj.2021108125","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/embj.2021108125\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/embj.2021108125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embj.2021108125.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:24:58Z","timestamp":1779308698000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/embj.2021108125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,7]]},"references-count":68,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2021,11,15]]}},"alternative-id":["BFEMBJ2021108125"],"URL":"https:\/\/doi.org\/10.15252\/embj.2021108125","relation":{},"ISSN":["0261-4189","1460-2075"],"issn-type":[{"value":"0261-4189","type":"print"},{"value":"1460-2075","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,7]]},"assertion":[{"value":"25 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMBJ2021108125"}}