Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes.
We show here that Vav-2 is tyrosine phosphorylated following antigen receptor engagement in both B- and T-cells, but potentiates nuclear factor of activated T cells (NFAT)-dependent transcription only in B cells. Vav-2 function requires the N-terminus, as well as functional Dbl homology and SH2 domains. More over, the enhancement of NFAT-dependent transcription by Vav-2 can be inhibited by a number of dominant-negative GTPases. The ability of Vav-2 to potentiate NFAT-dependent transcription correlates with its ability to promote a sustained calcium flux. Thus, Vav-2 augments the calcium signal in B cells but not T cells, and a truncated form of Vav-2 can neither activate NFAT nor augment calcium signaling. The CD19 co-receptor physically interacts with Vav-2 and synergistically enhances Vav-2 phosphorylation induced by the B-cell receptor (BCR). In addition, we found that Vav-2 augments CD19-stimulated NFAT- dependent transcription, as well as transcription from the CD5 enhancer. These data suggest a role for Vav-2 in transducing BCR signals to the transcription factor NFAT and implicate Vav-2 in the integration of BCR and CD19 signaling.
Doody
G M
GM
Lymphocyte Signaling and Development Laboratory, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.
Billadeau
D D
DD
Clayton
E
E
Hutchings
A
A
Berland
R
R
McAdam
S
S
Leibson
P J
PJ
Turner
M
M
D000818:Animals; D018941:Antigens, CD19 / Q000737:chemistry / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018956:CD5 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D051567:Proto-Oncogene Proteins c-vav; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D014443:Tyrosine / Q000737:chemistry
D018941:Antigens, CD19; D018956:CD5 Antigens; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors; C093651:VAV2 protein, human; C490565:Vav2 protein, mouse; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases