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Rac is involved in early TCR signaling

Arrieumerlou, C. and Randriamampita, C. and Bismuth, G. and Trautmann, A.. (2000) Rac is involved in early TCR signaling. Journal of immunology, Vol. 165, H. 6. pp. 3182-3189.

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Official URL: http://edoc.unibas.ch/dok/A5259791

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Abstract

The GTPase Rac controls signaling pathways often related to actin polymerization in various cell types. In T lymphocytes, Rac is activated by Vav, a major component of the multiprotein transduction complex associated to the TCR. Although profound signaling defects have been observed in Vav-deficient mice, a role of Rac in the corresponding early TCR signaling has not been tested directly. This question was investigated in Jurkat T cells transfected with either a dominant-negative (RacN17) or a constitutively active (RacV12) form of Rac. In T cells expressing either RacN17 or RacV12, the anti-CD3-induced Ca2+ response and production of inositol-1,4,5-trisphosphate were inhibited. The basal level of phosphatidylinositol-4,5-bisphosphate was not significantly diminished by Rac mutants. The major inhibitory effect of Rac mutants on Ca2+ signaling is exerted on the activity of phospholipase C-gamma and, before that, on the phosphorylation of ZAP-70 and of the linker molecule for activation of T cells, LAT. An anti-CD3-induced increase in actin polymerization was observed in control cells but not in cells transfected with a Rac mutant. In addition, latrunculin, which binds to monomeric actin, simultaneously inhibited basal and CD3-induced actin polymerization and Ca2+ signaling. These findings suggest a link between the effects exerted by Rac mutants on cortical actin polymerization and on TCR signaling. Rac cycling between its GTP- and GDP-bound states is necessary for this signaling. Alterations observed in early TCR-dependent signals suggest that Rac contributes to the assembly of the TCR-associated multiprotein transduction complex.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Molecular Microbiology (Arrieumerlou)
UniBasel Contributors:Arrieumerlou, C├ęcile
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Assoc. of Immunologists
ISSN:0022-1767
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:21
Deposited On:22 Mar 2012 13:23

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