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PP2A Dephosphorylates Elf-1 and Determines the Expression of CD3 and FcR in Human Systemic Lupus Erythematosus T Cells¹

Yuang-Taung Juang^2,*, Ying Wang, Guisen Jiang, Hai-Bin Peng^*, Sukran Ergin^*, Michelle Finnell^*, Abigail Magilavy^*, Vasileios C. Kyttaris^* and George C. Tsokos^2,*

^* Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910; and Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814

T cells from patients with systemic lupus erythematosus are characterized by decreased expression of CD3-chain and increased expression of FcR-chain, which becomes part of the CD3 complex and contributes to aberrant signaling. Elf-1 enhances the expression of CD3, whereas it suppresses the expression of FcR gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3 and FcR promoters. Suppression of the expression of the PP2A leads to increased expression of CD3 and decreased expression of FcR genes and correction of the early signaling response. Therefore, PP2A serves as a central determinant of abnormal T cell function in human lupus and may represent an appropriate treatment target.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R01AI42269, R01AI49954, and R01AI068787.

² Address correspondence and reprint requests to Drs. George C. Tsokos and Yuang-Taung Juang, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, E1CLS 957, Boston, MA 02115. E-mail addresses: gtsokos{at}bidmc.harvard.edu and yjuang{at}BIDMC.Harvard.edu

³ Abbreviations used in this paper: SLE, systemic lupus erythematosus; PKC, protein kinase C; AF, apoptotic fragment; CHX, cycloheximide; MS, mass spectrometry; PKN, protein kinase N; hnRNP, heterogeneous nuclear ribonucleoprotein; siRNA, small interfering RNA.