A 50-kDa ERK-like protein is up-regulated by a dual altered peptide ligand that suppresses myasthenia gravis-associated responses.
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.
Ben-David
Hava
H
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Aruna
Badiga Venkata
BV
Seger
Rony
R
Sela
Michael
M
Mozes
Edna
E
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D018655:Lymphocyte Count; D051379:Mice; D008970:Molecular Weight; D009157:Myasthenia Gravis / Q000201:enzymology* / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D010766:Phosphorylation / Q000187:drug effects; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D010455:Peptides; C514281:dual altered peptide ligand; D003208:Concanavalin A; D048049:Extracellular Signal-Regulated MAP Kinases