Abstract/Details

Dual roles for a p38 mitogen -activated protein kinase signaling module in immature B lymphomas: Transcriptional regulation and mediation of antigen-induced apoptosis


2000 2000

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Abstract (summary)

The studies presented herein examined the involvement of a p38 MAPK signaling module in B cell antigen receptor (BCR)-mediated phosphorylation and activation of CREB in the sIgM+ CH31 B cell lymphoma, which undergoes Ag-dependent cell death. The activity of p38 mitogen-activated protein kinase (MAPK) was transiently increased in response to BCR ligation. Phosphorylation of CREB on serine 133, a modification which results in trans-activation, was concurrently increased. Inhibition of p38 MAPK by treatment of CH31 B cells with the pyridinyl imidazole inhibitor, SB203580, reduced BCR-induced CREB phosphorylation. Previous studies from our laboratory have identified a role for CREB in regulating junB gene expression in mature B lymphocytes; it was determined whether p38 MAPK activity was necessary for CRE-dependent junB transcription in CH31 B cells. BCR ligation led to increased junB mRNA levels, which were significantly reduced in CH31 B cells pretreated with SB203580. Activation of a CRE-dependent junB promoter/CAT reporter gene by the BCR was also abrogated by SB203580. The findings implicate a p38 MAPK pathway in BCR-mediated CREB phosphorylation and junB transcriptional activation in phenotypically immature B cell lymphomas.

CH31 B lymphomas represent a model for antigen-induced tolerance of immature B lymphocytes, because cross-linking the B cell antigen receptor (BCR) induces G1 phase arrest and apoptosis. These data functionally characterize the role of p38 MAPK in BCR-induced apoptosis as well as evaluate the regulation of additional MAPKs by the BCR. JNK and ERK activities are not affected by BCR cross-linking. By contrast, pretreatment of CH31 B cells with the p38 MAPK inhibitor, SB203580 ablated both BCR-induced p38 MAPK activity and apoptosis. These findings establish a key role for p38 MAPK in antigen receptor-mediated apoptosis of CH31 B cells.

Indexing (details)


Subject
Molecular biology
Classification
0307: Molecular biology
Identifier / keyword
Biological sciences; Apoptosis; B lymphomas; CREB; Mitogen-activated protein kinase; p38 MAPK
Title
Dual roles for a p38 mitogen -activated protein kinase signaling module in immature B lymphomas: Transcriptional regulation and mediation of antigen-induced apoptosis
Author
Mataraza, Jennifer Marie
Number of pages
179
Publication year
2000
Degree date
2000
School code
0016
Source
DAI-B 61/11, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780493035437, 0493035435
Advisor
Chiles, Thomas C.
University/institution
Boston College
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
9995938
ProQuest document ID
304582611
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304582611/abstract
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