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Differential regulation of TCR-mediated gene transcription by Vav family members.

ABSTRACT: 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.

SUBMITTER: Zakaria S

PROVIDER: S-EPMC2211790 | biostudies-literature | 2004 Feb

REPOSITORIES: biostudies-literature

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Differential regulation of TCR-mediated gene transcription by Vav family members.

Zakaria Shaheen S Gomez Timothy S TS Savoy Doris N DN McAdam Simon S Turner Martin M Abraham Robert T RT Billadeau Daniel D DD

The Journal of experimental medicine 20040201 3

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 ...[more]

PMID: 14757747

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