A 50-kDa ERK-like protein is up-regulated by a dual altered peptide ligand that suppresses myasthenia gravis-associated responses.

Abstract

Myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG), are T cell-dependent antibody-mediated autoimmune diseases. A dual altered peptide ligand (APL) that is composed of the tandemly arranged two single amino acid analogues of two myasthenogenic peptides, p195-212 and p259-271, down-regulated in vitro and in vivo MG-associated autoreactive responses. The dual APL was shown to exert its beneficial effects by up-regulating ERK1,2 in CD4(+)CD25(+) regulatory cells. In this study, we investigated a novel 50-kDa ERK-like protein (ERK-50) that is up-regulated significantly in addition to ERK1,2 after treatment with the dual APL. We report here that ERK-50 was up-regulated in LN cells and in LN-derived T cells of mice that were immunized with the myasthenogenic peptides and treated with the dual APL. Moreover, ERK-50 was up-regulated in dual-APL- treated mice that were immunized with the Torpedo acetylcholine receptor. ERK-50 was demonstrated to be recognized by antibodies directed against the C and N termini of ERK1, against the C terminus of ERK2, and against general ERK. The 50-kDa ERK was shown to be stimulated by Con A, and inhibition of MEK1 down-regulated the 50-kDa ERK as was shown for ERK1,2. However, 4beta-phorbol 12-myristate 13-acetate (TPA) did not stimulate ERK-50. Finally, the activated ERK-50 was up-regulated in the dual-APL-induced CD4(+)CD25(+) regulatory cells. Thus, ERK-50 is suggested to be a novel ERK isoform, being up-regulated in response to treatment with the dual APL.

• Authors: Hava Ben-David, Badiga Venkata Aruna, Rony Seger, Michael Sela, Edna Mozes
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 103 Issue 48 Pg. 18232-7 (Nov 28 2006) ISSN: 0027-8424 [Print] United States
• PMID: 17108079 (Publication Type: Journal Article)

Chemical References

• Peptides
• dual altered peptide ligand
• Concanavalin A
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Cells, Cultured
• Concanavalin A (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Lymphocyte Count
• Mice
• Molecular Weight
• Myasthenia Gravis (enzymology, immunology)
• Peptides (immunology)
• Phosphorylation (drug effects)
• Sensitivity and Specificity
• T-Lymphocytes (cytology, drug effects, immunology, metabolism)
• Up-Regulation