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Involvement of phosphoinositide 3-kinase and Rac in membrane ruffling induced by IL-2 in T cells

Arrieumerlou, C. and Donnadieu, E. and Brennan, P. and Keryer, G. and Bismuth, G. and Cantrell, D. and Trautmann, A.. (1998) Involvement of phosphoinositide 3-kinase and Rac in membrane ruffling induced by IL-2 in T cells. European Journal of Immunology, Vol. 28, H. 6. pp. 1877-1885.

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Official URL: http://edoc.unibas.ch/dok/A5259793

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Abstract

IL-2 is known to play a critical role in regulating T lymphocyte proliferation. We show here that IL-2 also provokes an instantaneous and sustained membrane ruffling in cloned human or murine T cells as well as in lectin-activated peripheral blood lymphocytes. In the IL-2-induced lamellipodia, tubulin is depolymerized whereas actin is strongly polymerized, forming caps. IL-2-induced membrane ruffling is protein kinase C (PKC) independent, as judged by the absence of effects of bisindolylmaleimide, an efficient inhibitor of all PKC isoforms. The formation of lamellipodia by IL-2 is blocked by wortmannin and LY294002, two inhibitors of phosphoinositide 3-kinase (PI3-kinase). Moreover, expression in murine T cells of an inactive form of P13-kinase inhibits IL-2-induced membrane ruffling, whereas expression of a constitutively active p110 increases the basal membrane ruffling. Rac is also involved in IL-2-induced membrane ruffling since an inactive form of Rac (N17rac) blocks the IL-2-induced lamellipodia, whereas the constitutive form of Rac (Val12rac) can also lead to membrane ruffling. In the signaling cascade, Rac is downstream of PI3-kinase since constitutive membrane ruffling in Val12rac cells is insensitive to wortmannin. Thus, through a signaling cascade involving PI3-kinase and Rac, IL-2 can induce profound alterations of the T cell cytoskeleton, a phenomenon which might be of importance for T cell physiology.
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:Verl. Chemie
ISSN:0014-2980
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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