c-Jun and Ets2 proteins regulate expression of spleen tyrosine kinase in T cells.

The Journal of Biological Chemistry
Debjani GhoshVasileios C Kyttaris

Abstract

Effector T cells and T cells from patients with systemic lupus erythematosus (SLE) express increased levels of the spleen tyrosine kinase (Syk). Syk binds to the T cell receptor (TCR)-CD3 complex and transduces the TCR-mediated signal in the cell more efficiently than the canonical CD3ζ chain. The reasons for the increased expression of Syk are unclear. In the present study, we found that Syk is regulated by the transcription factor c-Jun in cooperation with Ets2. c-Jun and Ets2 bound to the SYK promoter in close proximity and increased the promoter activity in a specific manner. Disruption of c-Jun and Ets2 expression by siRNA resulted in decreased expression of Syk. Overexpression of c-Jun but not Ets2 resulted in increase in Syk protein. c-Jun and Ets2 co-immunoprecipitated and had an additive effect on Syk expression. c-Jun-driven SYK promoter activation showed a similar pattern in B cells; however, as expected, basal promoter activity was much higher in B cells as compared with T cells. Overexpression of c-Jun led to increase in intracytoplasmic calcium flux following TCR stimulation. Moreover, we found that SLE T cells had increased levels of c-Jun at baseline and phosphorylated c-Jun upon activation. Finally, disruption ...Continue Reading

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Citations

Sep 10, 2013·PloS One·Alexandros P GrammatikosGeorge C Tsokos
May 28, 2014·Journal of Immunology Research·Anselm Mak, Nien Yee Kow
Jul 4, 2012·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·D SantovitoF Cipollone
Oct 24, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Fang YaoXiaochun Bai
Mar 24, 2020·Cellular & Molecular Immunology·Sarang TarteyThirumala-Devi Kanneganti

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