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Title: | RGS10 restricts upregulation by chemokines of T cell adhesion mediated by α4β1 and αLβ2 Integrins. |
Authors: | García-Bernal, David ![]() ![]() ![]() ![]() |
Issue Date: | 1-Aug-2011 |
Publisher: | American Association of Immunologists |
Citation: | Journal of Immunology 187(3):1264-72(2011) |
Abstract: | Chemokines rapidly and transiently upregulate α4β1 and αLβ2 integrin-mediated adhesion during T lymphocyte extravasation by activating Gα-dependent inside-out signaling. To limit and terminate Gα-mediated signaling, cells can use several mechanisms, including the action of regulator of G protein signaling (RGS) proteins, which accelerate the GTPase activity of Gα subunits. Using human T cells silenced for or overexpressing RGS10, we show in this article that RGS10 functions as an inhibitor of Gαi-dependent, chemokine-upregulated T cell adhesion mediated by α4β1 and αLβ2. Shear stress-dependent detachment and cell spreading analyses revealed that RGS10 action mainly targets the adhesion strengthening and spreading phases of α4β1-mediated cell attachment. Associated with these observations, chemokine-stimulated Vav1–Rac1 activation was longer sustained and of higher intensity in RGS10-silenced T cells, or inhibited in cells overexpressing RGS10. Of importance, expression of constitutively activated Rac1 forms in cells overexpressing RGS10 led to the rescue of CXCL12-stimulated adhesion to VCAM-1 to levels similar to those in control transfectants. Instead, adhesion under flow conditions, soluble binding experiment, flow cytometry, and biochemical analyses revealed that the earlier chemokine-triggered integrin activation step was mostly independent of RGS10 actions. The data strongly suggest that RGS10 opposes activation by chemokines of the Vav1–Rac1 pathway in T cells, leading to repression of adhesion strengthening mediated by α4β1. In addition to control chemokine-upregulated T cell attachment, RGS10 also limited adhesion-independent cell chemotaxis and activation of cdc42. These results identify RGS10 as a key molecule that contributes to the termination of Gα-dependent signaling during chemokine-activated α4β1- and αLβ2-dependent T cell adhesion |
Description: | 9 páginas, 6 figuras -- PAGS nros. 1264-1272 |
Publisher version (URL): | http:dx.doi.org/10.4049/jimmunol.1002960 |
URI: | http://hdl.handle.net/10261/51105 |
DOI: | 10.4049/jimmunol.1002960 |
ISSN: | 0022-1767 |
E-ISSN: | 1550-6606 |
Appears in Collections: | (CIB) Artículos |
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