Differential regulation of TCR-mediated gene transcription by Vav family members.
Although all three Vav family members are expressed in T lymphocytes, the role that Vav3 plays in T cell activation is poorly defined. Here we show that, like Vav1, Vav3 undergoes rapid tyrosine phosphorylation after T cell receptor (TCR) cross-linkage and interacts with the adaptor molecules SLP76 and 3BP2 in a SH2-dependent manner. However, depletion of Vav1 but not Vav3 protein by RNA interference affects TCR-mediated IL-2 promoter activity. In contrast, Vav3 function is specifically required for coupling TCR stimulation to serum response element-mediated gene transcription. These data indicate that, although both Vav proteins are biochemically coupled to the TCR, they regulate distinct molecular pathways leading to defined gene transcriptional events.
Zakaria
Shaheen
S
Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Gomez
Timothy S
TS
Savoy
Doris N
DN
McAdam
Simon
S
Turner
Martin
M
Abraham
Robert T
RT
Billadeau
Daniel D
DD
D018797:Cell Cycle Proteins; D005786:Gene Expression Regulation / Q000276:immunology; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D019169:Jurkat Cells; D015513:Oncogene Proteins / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000276:immunology; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology
D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C496618:VAV1 protein, human; C093651:VAV2 protein, human; C496621:VAV3 protein, human