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Differential activation and regulation of mitogen activated protein kinases through the antigen receptor and CD40 in human B cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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1999 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 29, no 9, 2999-3008 p.Article in journal (Refereed) Published
Abstract [en]

In human B cells, antigen receptor ligation and CD40 ligation are known to activate the extracellular-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) pathways, which in turn regulate many important B cell functions. We previously reported that antigen receptor ligation activated the ERK pathway whereas CD40 ligation activated the JNK/stress-activated protein kinase (SAPK) pathway. Here, we demonstrate that another SAPK, p38/Hog1, is activated by both antigen receptor ligation or CD40 ligation in a human B-lymphoblastoid cell line and tonsillar B cells. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, partially inhibited ERK2 and p38 activation triggered through the B cell receptor whereas activation of JNK1 and p38 through CD40 was not affected. PD98059, a specific inhibitor of mitogen-activated extracellular response kinase kinase (MEK), significantly inhibited ERK2 activation and partially inhibited p38 activation triggered by anti-IgM antibody treatment, but did not affect CD40-dependent signaling events. In addition, anti-IgM antibody-induced signaling pathways were shown to be PKC-dependent in contrast to the CD40-induced signaling pathways. Thus, the B cell receptor and CD40 recruit the ERK, JNK and p38 pathways by using different upstream effectors.

Place, publisher, year, edition, pages
1999. Vol. 29, no 9, 2999-3008 p.
Keyword [en]
B cell receptor, Activation
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-51578DOI: 10.1002/(SICI)1521-4141(199909)29:09<2999::AID-IMMU2999>3.0.CO;2-LPubMedID: 10508274OAI: oai:DiVA.org:uu-51578DiVA: diva2:79487
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2011-06-28Bibliographically approved

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Gerwins, Pär
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