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

Arrieumerlou, C., Donnadieu, E., Brennan, Paul ORCID:, Keryer, G., Bismuth, G., 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 28 (6) , pp. 1877-1885. 10.1002/(SICI)1521-4141(199806)28:06<1877::AID-IMMU1877>3.0.CO;2-I

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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 PIS-kinase inhibits IL-2-induced membrane ruffling, whereas expression of a constitutively active p110 increases the basal membrane ruffling. Rac is also involved in IL2-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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: T lymphocyte;Phosphoinositide 3-kinase;Rac;IL-2;Cytoskeleton
Publisher: Wiley-Blackwell
ISSN: 0014-2980
Last Modified: 25 Oct 2022 09:05

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