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Pleiotropic defects in TCR signaling in a Vav‐1‐null Jurkat T‐cell line
Author(s) -
Cao Youjia,
Janssen Erin M.,
Duncan Andrew W.,
Altman Am,
Billadeau Daniel D.,
Abraham Robert T.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf499
Subject(s) - library science , jurkat cells , medicine , t cell , immunology , computer science , immune system
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.Vav1 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.Vav1 cells display a selective defect in sustained Ca 2+ 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.Vav1 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.