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

TY - JOUR

T1 - Involvement of phosphoinositide 3-kinase and Rac in membrane ruffling induced by IL-2 in T cells

AU - Arrieumerlou, Cécile

AU - Donnadieu, Emmanuel

AU - Brennan, Paul

AU - Keryer, Guy

AU - Bismuth, Georges

AU - Cantrell, Doreen

AU - Trautmann, Alain

PY - 1998/6

Y1 - 1998/6

N2 - 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 PI3-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.

AB - 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 PI3-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.

KW - Cytoskeleton

KW - IL-2

KW - Phosphoinositide 3-kinase

KW - Rac

KW - T lymphocyte

UR - https://www.scopus.com/pages/publications/0031841211

U2 - 10.1002/(SICI)1521-4141(199806)28:06<1877::AID-IMMU1877>3.0.CO;2-I

DO - 10.1002/(SICI)1521-4141(199806)28:06<1877::AID-IMMU1877>3.0.CO;2-I

M3 - Article

C2 - 9645369

AN - SCOPUS:0031841211

SN - 0014-2980

VL - 28

SP - 1877

EP - 1885

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 6

ER -