Abstract
AbstractThe 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-γ 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.
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Dates
Type | When |
---|---|
Created | 11 years, 4 months ago (April 20, 2014, 9:30 p.m.) |
Deposited | 7 months, 3 weeks ago (Jan. 2, 2025, 1:38 p.m.) |
Indexed | 4 months, 4 weeks ago (March 30, 2025, 4:27 a.m.) |
Issued | 24 years, 11 months ago (Sept. 15, 2000) |
Published | 24 years, 11 months ago (Sept. 15, 2000) |
Published Print | 24 years, 11 months ago (Sept. 15, 2000) |
@article{Arrieumerlou_2000, title={Rac Is Involved in Early TCR Signaling}, volume={165}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.165.6.3182}, DOI={10.4049/jimmunol.165.6.3182}, number={6}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Arrieumerlou, Cécile and Randriamampita, Clotilde and Bismuth, Georges and Trautmann, Alain}, year={2000}, month=sep, pages={3182–3189} }