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

J Recept Signal Transduct Res. 2006;26(1-2):87-106. doi: 10.1080/10799890600567372.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Actins
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Depsipeptides
  • Gout Suppressants
  • Interleukin-2
  • Mitogens
  • Nucleic Acid Synthesis Inhibitors
  • Phytohemagglutinins
  • Receptors, Interleukin-2
  • Tubulin
  • jasplakinolide
  • Cytochalasin D
  • Paclitaxel
  • Colchicine