Tubulin polymerization modulates interleukin-2 receptor signal transduction in human T cells

• Published in: Journal of receptors and signal transduction Vol. 26; no. 1-2; p. 87
• Main Authors: Goebel, Jens, Forrest, Kathy, Wills-Karp, Marsha, Roszman, Thomas L
• Format: Journal Article
• Language: English
• Published: England 2006
• Subjects: Actins - metabolism; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents, Phytogenic - pharmacology; Colchicine - pharmacology; Cytochalasin D - pharmacology; Cytoskeleton - metabolism; Depsipeptides - pharmacology; Gout Suppressants - pharmacology; Humans; Interleukin-2 - pharmacology; Mice; Mice, Transgenic; Mitogens - pharmacology; Nucleic Acid Synthesis Inhibitors - pharmacology; Paclitaxel - pharmacology; Phytohemagglutinins - pharmacology; Receptors, Interleukin-2 - metabolism; Signal Transduction; T-Lymphocytes - metabolism; Tubulin - metabolism
• ISSN: 1079-9893
• DOI: 10.1080/10799890600567372

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.