Bibliographic Details
| Title: |
Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus. |
| Authors: |
Yang, Mei-Ling, Lam, TuKiet T., Kanyo, Jean, Kang, Insoo, Zhou, Zhaohui Sunny, Clarke, Steven G., Mamula, Mark J. |
| Source: |
Autoimmunity; 2023, Vol. 56 Issue 1, p1-13, 13p |
| Subject Terms: |
T cells, PROTEIN-tyrosine kinases, POST-translational modification, SYSTEMIC lupus erythematosus, ANTIGEN receptors, METHYLGUANINE |
| Abstract: |
Protein posttranslational modifications (PTMs) arise in a number of normal cellular biological pathways and in response to pathology caused by inflammation and/or infection. Indeed, a number of PTMs have been identified and linked to specific autoimmune responses and metabolic pathways. One particular PTM, termed isoaspartyl (isoAsp or isoD) modification, is among the most common spontaneous PTM occurring at physiological pH and temperature. Herein, we demonstrate that isoAsp modifications arise within the ZAP70 protein tyrosine kinase upon T-cell antigen receptor (TCR) engagement. The enzyme protein L-isoaspartate O-methyltransferase (PCMT1, or PIMT, EC 2.1.1.77) evolved to repair isoaspartyl modifications in cells. In this regard, we observe that increased levels of isoAsp modification that arise under oxidative stress are correlated with reduced PIMT activity in patients with systemic lupus erythematosus (SLE). PIMT deficiency leads to T cell hyper-proliferation and hyper-phosphorylation through ZAP70 signaling. We demonstrate that inducing the overexpression of PIMT can correct the hyper-responsive phenotype in lupus T cells. Our studies reveal a phenotypic role of isoAsp modification and phosphorylation of ZAP70 in lupus T cell autoimmunity and provide a potential therapeutic target through the repair of isoAsp modification. [ABSTRACT FROM AUTHOR] |
|
Copyright of Autoimmunity is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
|
Full text is not displayed to guests. |
Login for full access.
|
