title: Vav1 is a component of transcriptionally active complexes.
abstract: 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.
authors: Unité Inserm 363, Oncologie Cellulaire et Moléculaire, Institut Cochin de Génétique Moléculaire, Hopital Cochin, Paris 75014, France.
authors: Martin
authors: M
authors: Houlard
authors: Ramachandran
authors: R
authors: Arudchandran
authors: Fabienne
authors: F
authors: Regnier-Ricard
authors: Antonia
authors: A
authors: Germani
authors: Sylvie
authors: S
authors: Gisselbrecht
authors: Ulrich
authors: U
authors: Blank
authors: Juan
authors: J
authors: Rivera
authors: Nadine
authors: N
authors: Varin-Blank
mesh_terms: 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
chemical_list: 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