TY - JOUR
T1 - Tubulin polymerization modulates interleukin-2 receptor signal transduction in human T cells
AU - Goebel, Jens
AU - Forrest, Kathy
AU - Wills-Karp, Marsha
AU - Roszman, Thomas L.
N1 - Funding Information:
This work was supported by the Department of Pediatrics, University of Kentucky, by a Physician-Scientist Award to J.G. from the University of Kentucky Hospital, by a Bristol Myers Squibb Young Investigator Award to J.G. from the National Kidney Foundation, and by National Institutes of Health grant 5KO8AI049241 to J.G. We acknowledge the excellent technical support by Jennifer Strange and Greg Bauman (University of Kentucky Flow Cytometry Core Facility) and the outstanding secretarial support by Judy Howard (Nephrology and Hypertension Division, Cincinnati Children’s Hospital Medical Center).
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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 β-chain and enhanced the association of the IL-2R γ-chain with cytoskeletal tubulin. The IL-2R β-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 DO11.10 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.
AB - 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 β-chain and enhanced the association of the IL-2R γ-chain with cytoskeletal tubulin. The IL-2R β-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 DO11.10 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.
KW - Actin and tubulin polymerization
KW - Human T cells
KW - Interleukin-2 receptor signal transduction
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U2 - 10.1080/10799890600567372
DO - 10.1080/10799890600567372
M3 - Article
C2 - 16595340
AN - SCOPUS:33645763252
SN - 1079-9893
VL - 26
SP - 87
EP - 106
JO - Journal of Receptors and Signal Transduction
JF - Journal of Receptors and Signal Transduction
IS - 1-2
ER -