Vav1 is a component of transcriptionally active complexes.
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)kappaB-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 NFkappaB-like transcriptional activity.
Houlard
Martin
M
Unité Inserm 363, Oncologie Cellulaire et Moléculaire, Institut Cochin de Génétique Moléculaire, Hopital Cochin, Paris 75014, France.
Arudchandran
Ramachandran
R
Regnier-Ricard
Fabienne
F
Germani
Antonia
A
Gisselbrecht
Sylvie
S
Blank
Ulrich
U
Rivera
Juan
J
Varin-Blank
Nadine
N
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D011519:Proto-Oncogenes; D017455:Receptors, IgE / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D018909:src Homology Domains
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D017455:Receptors, IgE; D014157:Transcription Factors; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse