Tubulin polymerization modulates interleukin-2 receptor signal transduction in human T cells.
Few data exist on the modulation of cytokine receptor signaling by the actin or tubulin cytoskeleton. Therefore, we studied interleukin-2 receptor (IL-2R) signaling in phytohemagglutinine (PHA)-pretreated human T cells in the context of alterations in the cytoskeletal system induced by cytochalasin D (CyD), jasplaklinolide (Jas), taxol (Tax), or colchicine (Col). We found that changes in cytoskeletal tubulin polymerization altered the strength of several IL-2-triggered signals. Moreover, Tax-induced tubulin hyperpolymerization augmented the surface expression of the IL-2R ss -chain and enhanced the association of the IL-2R beta -chain with cytoskeletal tubulin. The IL-2R beta-chain, in turn, was constitutively associated with tubulin and, more weakly, actin. To exclude the possibility that these associations are artifacts caused by PHA, we confirmed them in T cells from TCR-transgenic DO 11.10 mice stimulated with their nominal antigen. We conclude that altered polymerization of cytoskeletal components, especially tubulin, is accompanied by modulation of IL-2 signaling at the receptor level.
Goebel
Jens
J
Department of Pediatrics, University of Kentucky, Lexington, Kentucky, USA. Jens.Goebel@cchmc
Forrest
Kathy
K
Wills-Karp
Marsha
M
Roszman
Thomas L
TL
D000199:Actins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology; D006074:Gout Suppressants / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*
D000199:Actins; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D047630:Depsipeptides; D006074:Gout Suppressants; D007376:Interleukin-2; D008934:Mitogens; D019384:Nucleic Acid Synthesis Inhibitors; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D014404:Tubulin; C057531:jasplakinolide; D015638:Cytochalasin D; D017239:Paclitaxel; D003078:Colchicine