The Journal of Experimental Medicine
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Published 6 May 2002. doi:10.1084/jem.20011701
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© Rockefeller University Press, 0022-1007/2002/5/1115/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 9, May 6, 2002 1115-1127

Vav1 Is a Component of Transcriptionally Active Complexes

Martin Houlard1, Ramachandran Arudchandran2, Fabienne Regnier-Ricard1, Antonia Germani1, Sylvie Gisselbrecht1, Ulrich Blank3, Juan Rivera2 and Nadine Varin-Blank1

1 Unité Inserm 363, Oncologie Cellulaire et Moléculaire, Institut Cochin de Génétique Moléculaire, Hopital Cochin, Paris 75014, France
2 Molecular Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
3 Unité d'Immuno-allergie, Institut Pasteur, Paris 75015, France

Address correspondence to Dr. N. Varin-Blank, U363 Inserm, ICGM, Hopital Cochin, 27 rue du Fg St Jacques, 75014 Paris, France. Phone: 33-1-40-51-65-40; Fax: 33-1-40-57-65-70; E-mail: varin{at}cochin.inserm.fr, and Dr. J. Rivera, NIAMS, NIH, Bg 10 Room 9N-228, Bethesda, MD 20892. Phone: 301-496-7592; Fax: 301-480-1580; E-mail: juan_rivera{at}nih.gov

The importance of the hematopoietic protooncogene Vav1 in immune cell function is widely recognized, although its regulatory mechanisms are not completely understood. Here, we examined whether Vav1 has a nuclear function, as past studies have reported its nuclear localization. Our findings provide a definitive demonstration of Vav1 nuclear localization in a receptor stimulation–dependent manner and reveal a critical role for the COOH-terminal Src homology 3 (SH3) domain and a nuclear localization sequence within the pleckstrin homology domain. Analysis of DNA-bound transcription factor complexes revealed nuclear Vav1 as an integral component of transcriptionally active nuclear factor of activated T cells (NFAT)- and nuclear factor (NF){kappa}B-like complexes, and the COOH-terminal SH3 domain as being critical in their formation. Thus, we describe a novel nuclear role for Vav1 as a component and facilitator of NFAT and NF{kappa}B-like transcriptional activity.

Key Words: Vav • nuclear translocation • nuclear factor of activated T cells • calcium influx • protein subdomains


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