期刊
MOLECULAR IMMUNOLOGY
卷 44, 期 9, 页码 2469-2480出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2006.09.024
关键词
gelsolin; T cells; signal transduction; cytoskeleton; lipid rafts
资金
- Intramural NIH HHS Funding Source: Medline
- NCI NIH HHS [T32 CA009141, T32 CA009141-24, T32 CA09141, T32 CA009141-23] Funding Source: Medline
Upon T cell receptor engagement, both the actin cytoskeleton and substrates of tyrosine phosphorylation are remodeled to create a signaling complex at the interface of the antigen-presenting cell and responding T cell. While T cell signaling has been shown to regulate actin reorganization, the mechanisms by which changes in actin dynamics affect early T cell signaling have not been fully explored. Using gelsolin, an actin-binding protein with capping and severing activities, and latrunculin, an actin-depolymerizing agent, we have further investigated the interplay between actin dynamics and the regulation of T cell signaling. Overexpression of gelsolin altered actin dynamics in Jurkat T cells, and alteration of actin dynamics correlated with dysregulation of tyrosine phosphorylation of raft-associated substrates. This perturbation of tyrosine phosphorylation was correlated with inhibition of activation-dependent signaling pathways regulating Erk-1/2 phosphorylation, NF-AT transcriptional activation and IL-2 production. Modification of actin by the depolymerizing agent latrunculin also altered the tyrosine phosphorylation patterns of proteins associated with lipid rafts, and pre-treatment with latrunculin inhibited anti-CD3 mAb-mediated NF-AT activation. Thus, our data indicate that actin cytoskeletal dynamics modulate the tyrosine phosphorylation of raft-associated proteins and subsequent downstream signal transduction. (c) 2006 Elsevier Ltd. All rights reserved.
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