Pleiotropic defects in TCR signaling in a Vav-1-null Jurkat T-cell line

Youjia Cao, Erin M. Janssen, Andrew W. Duncan, Amnon Altman, Daniel D Billadeau, Robert T. Abraham

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

The Rac/Rho-specific guanine nucleotide exchange factor, Vav-1, is a key component of the T-cell antigen receptor (TCR)-linked signaling machinery. Here we have used somatic cell gene-targeting technology to generate a Vav-1-deficient Jurkat T-cell line. The J.Vavl cell line exhibits dramatic defects in TCR-dependent interleukin (IL)-2 promoter activation, accompanied by significant reductions in the activities of the NFAT(IL-2), NFκB, AP-1 and REAP transcription factors that bind to the IL-2 promoter region. In contrast, loss of Vav-1 had variable effects on early TCR-stimulated signaling events. J.Vavl cells display a selective defect in sustained Ca2+ signaling during TCR stimulation, and complementation of this abnormality by exogenously introduced Vav-1 is dependent on the Vav-1 calponin homology domain. While JNK activation was severely impaired, the stimulation of Ras, ERK and protein kinase C-θ activities, as well as the mobilization of lipid rafts, appeared normal in the J.Vavl cells. Finally, evidence is presented to suggest that the alternative Vav family members, Vav-2 and Vav-3, are activated during TCR ligation, and partially compensate for the loss of Vav-1 in Jurkat T cells.

Original languageEnglish (US)
Pages (from-to)4809-4819
Number of pages11
JournalEMBO Journal
Volume21
Issue number18
DOIs
StatePublished - Sep 16 2002
Externally publishedYes

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Keywords

  • protein kinase C-θ
  • signal transduction
  • T-cell antigenreceptor
  • Vav

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Cao, Y., Janssen, E. M., Duncan, A. W., Altman, A., Billadeau, D. D., & Abraham, R. T. (2002). Pleiotropic defects in TCR signaling in a Vav-1-null Jurkat T-cell line. EMBO Journal, 21(18), 4809-4819. https://doi.org/10.1093/emboj/cdf499