The golli-myelin basic protein negatively regulates signal transduction in T lymphocytes

被引:40
作者
Feng, JM [1 ]
Fernandes, AO [1 ]
Campagnoni, CW [1 ]
Hu, YH [1 ]
Campagnoni, AT [1 ]
机构
[1] Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Los Angeles, CA 90024 USA
关键词
T lymphocytes; cellular activation; protein kinase C; Golli-MBP;
D O I
10.1016/j.jneuroim.2004.03.021
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Protein kinase C (PKC) plays a critical role in signal transduction controlling T lyruphocyte activation. Both positive and negative regulation of signal transduction is needed for proper control of T lymphocyte activation. We have found that a golli product of the myelin basic protein (MBP) gene can serve as a negative regulator of signaling pathways in the T lymphocyte, particularly the PKC pathway. Increased expression of golli BG21 in Jurkat T cells strongly inhibits anti-CD3epsilon-induced IL-2-luciferase activity, an indicator of T lymphocyte activation. Golli BG21 can be phosphorylated by PKC in vitro and its phosphorylation increases in PMA-activated Jurkat cells. BG21 inhibits the PMA-induced increase in AP-1 or NF-kappaB activation, consistent with golli acting in a PKC-mediated cellular event. Golli BG21 inhibition of the PKC pathway is not due to a direct action on PKC activation but in the cascade following PKC activation, since BG21 neither reduces PKC enzyme activity nor blocks the membrane association of PKCtheta brought on by T lymphocyte activation. The inhibitory function of BG21 is independent of its phosphorylation by PKC because a mutant BG21, in which the PKC sites have been mutated, is as effective as the wild type BG21 in inhibiting the PMA-induced AP-1 activation. Structure-function assays indicate that BG21 inhibitory activity resides in the golli domain rather than in MBP domain of the molecule. These results reveal a novel role for MBP gene products in T lymphocytes within the immune system. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:57 / 66
页数:10
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