Differential activation and regulation of mitogen activated protein kinases through the antigen receptor and CD40 in human B cells
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
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.
B cell receptor, Activation
Medical and Health Sciences
IdentifiersURN: 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