Abstract
Cross-linking of the B cell receptor (BCR) on the immature B lymphoma cell line BKS-2 induces growth inhibition and apoptosis accompanied by rapid down-regulation of the immediate-early gene egr-1. In these lymphoma cells, egr-1 is expressed constitutively and has a prosurvival role, as Egr-1-specific antisense oligonucleotides or expression of a dominant-negative inhibitor of Egr-1 also prevented the growth of BKS-2 cells. Moreover, enhancement of Egr-1 protein with phorbol 12-myristate 13-acetate or an egr-1 expression vector rescued BKS-2 cells from BCR signal-induced growth inhibition. Nuclear run-on and mRNA stability assays indicated that BCR-derived signals act at the transcriptional level to reduce egr-1 expression. Inhibitors of ERK and JNK (but not of p38 MAPK) reduced egr-1 expression at the protein level. Transcriptional regulation appears to have a role because egr-1 promoter-driven luciferase expression was reduced by ERK and JNK inhibitors. Promoter truncation experiments suggested that several serum response elements are required for MAPK-mediated egr-1 expression. Our study suggests that BCR signals reduce egr-1 expression by inhibiting activation of ERK and JNK. Unlike ERK and JNK, p38 MAPK reduces constitutive expression of egr-1. Unlike the immature B lymphoma cells, normal immature B cells did not exhibit constitutive MAPK activation. BCR-induced MAPK activation was modest and transient with a small increase in egr-1 expression in normal immature B cells consistent with their inability to proliferate in response to BCR cross-linking.
Document Type
Article
Publication Date
10-24-2006
Digital Object Identifier (DOI)
https://doi.org/10.1074/jbc.M604671200
Funding Information
This work was supported by National Institutes of Health Grant 5P01CA092372 (to S. B.). 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.
Repository Citation
Ke, Jiyuan; Gururajan, Murali; Kumar, Anupam; Simmons, Alan; Turcios, Lilia; Chelvarajan, Ralph Lakshman; Cohen, David M.; Wiest, David L.; Monroe, John G.; and Bondada, Subbarao, "The Role of MAPKs in B Cell Receptor-Induced Down-Regulation of Egr-1 in Immature B Lymphoma Cells" (2006). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 119.
https://uknowledge.uky.edu/microbio_facpub/119
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Medical Immunology Commons, Medical Microbiology Commons, Molecular Genetics Commons
Notes/Citation Information
Published in The Journal of Biological Chemistry, v. 281, no. 52, p. 39806-39818.
This research was originally published in The Journal of Biological Chemistry. Jiyuan Ke, Murali Gururajan, Anupam Kumar, Alan Simmons, Lilia Turcios, Ralph L. Chelvarajan, David M. Cohen, David L. Wiest, John G. Monroe, and Subbarao Bondada. The Role of MAPKs in B Cell Receptor-induced Down-regulation of Egr-1 in Immature B Lymphoma Cells. J. Biol. Chem. 2006; 281:39806-39818. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
The copyright holder has granted the permission for posting the article here.