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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Active Transport, Cell Nucleus
-
Animals
-
Binding Sites
-
Bone Marrow Cells / cytology
-
Bone Marrow Cells / physiology
-
Cell Cycle Proteins*
-
Cell Nucleus / physiology
-
Cells, Cultured
-
DNA Primers
-
DNA-Binding Proteins / metabolism
-
Humans
-
Interleukin-2 / genetics
-
Mice
-
Mice, Knockout
-
NFATC Transcription Factors
-
Nuclear Proteins*
-
Polymerase Chain Reaction
-
Promoter Regions, Genetic
-
Proto-Oncogene Proteins / deficiency
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism*
-
Proto-Oncogene Proteins c-vav
-
Proto-Oncogenes
-
Receptors, IgE / immunology
-
Transcription Factors / metabolism*
-
Transcription, Genetic*
-
src Homology Domains
Substances
-
Cell Cycle Proteins
-
DNA Primers
-
DNA-Binding Proteins
-
Interleukin-2
-
NFATC Transcription Factors
-
Nuclear Proteins
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-vav
-
Receptors, IgE
-
Transcription Factors
-
VAV1 protein, human
-
Vav1 protein, mouse