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

Cécile Arrieumerlou, Emmanuel Donnadieu, Paul Brennan, Guy Keryer, Georges Bismuth, Doreen Cantrell, Alain Trautmann

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1877-1885
Number of pages9
JournalEuropean Journal of Immunology
Volume28
Issue number6
DOIs
Publication statusPublished - Jun 1998

Keywords

  • Cytoskeleton
  • IL-2
  • Phosphoinositide 3-kinase
  • Rac
  • T lymphocyte

Fingerprint Dive into the research topics of 'Involvement of phosphoinositide 3-kinase and Rac in membrane ruffling induced by IL-2 in T cells'. Together they form a unique fingerprint.

Cite this