Paxillin在T細胞活化上角色之探討
The Role of the Adaptor Protein Paxillin in T Cell Activation
Date Issued
2005
Date
2005
Author(s)
Chang, An-Yun
DOI
zh-TW
Abstract
Paxillin is one of the important adaptor proteins down stream of integrin. Integrin supports the association of T cell and antigen presenting cell, and provides co-stimulatory signal during T cell activation. It is known that during T cell activation, paxillin is phosphorylated and recruited to the site of immunological synapse. However, the exact role of paxillin in T cell activation has not been defined. In this study, we elucidated the role of paxillin in T cell activation, by expressing different paxillin phosphorylation site mutant in DO11.10 hybridoma. We also examined the role of paxillin in normal T cell activation and development, by expressing S178A/S85A paxillin double phosphorylation site mutant in transgenic mice.
Results from our study demonstrate that overexpression of paxillin with mutation at single phosphorylation site targeted by FAK, JNK, or p38 in DO11.10 hybridoma did not affect T cell activation, as measured by IL-2 production or T cell-antigen presenting cell conjugation. Expression of paxillin with mutation at double phosphorylation site in different combination, resulted in decreased IL-2 production upon TCR stimulation. Expression of paxillin with mutation at double phosphorylation site targeted by JNK and p38 (S178A/S85A), led to the most significant reduction of IL-2 generation. However, T cell-antigen presenting cell conjugation was not altered by expression of paxillin with mutation at double phosphorylation sites.
To study the role of paxillin in T cell activation and development in normal T cells, we further generated paxillin S178A/S85A transgenic mice. In comparison with normal littermate control mice, transgenic mice showed defects in T cell development, with reduction in thymic single positive T cell population and in splenic CD4 T cell population. Thymocytes and splenic T cells from S178A/S85A-paxillin transgenic mice, displayed attenuated cell proliferation as well as IL-2 production during TCR stimulation.
In summary, mutation of paxillin at phosphorylation sites targeted by combination of p38MAPK, JNK, or FAK clearly inhibited activation of T cell line. In addition, blockage of paxillin phosphorylation by p38MAPK and JNK suppressed activation and development of normal T cells. Our results indicate that phosphorylation of paxillin by different kinases, especially p38MAPK and JNK, is essential for T cell activation and T cell development.
Subjects
T細胞
活化
Paxillin
T cell
activation
Type
other
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