The role of MAPKs in B cell receptor-induced down-regulation of Egr-1 in immature B lymphoma cells

Jiyuan Ke, Murali Gururajan, Anupam Kumar, Alan Simmons, Lilia Turcios, Ralph L. Chelvarajan, David M. Cohen, David L. Wiest, John G. Monroe, Subbarao Bondada

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)39806-39818
Number of pages13
JournalJournal of Biological Chemistry
Volume281
Issue number52
DOIs
StatePublished - Dec 29 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ke, J., Gururajan, M., Kumar, A., Simmons, A., Turcios, L., Chelvarajan, R. L., Cohen, D. M., Wiest, D. L., Monroe, J. G., & Bondada, S. (2006). The role of MAPKs in B cell receptor-induced down-regulation of Egr-1 in immature B lymphoma cells. Journal of Biological Chemistry, 281(52), 39806-39818. https://doi.org/10.1074/jbc.M604671200