Ligation of CD40 receptor in human B lymphocytes triggers the 5-lipoxygenase pathway to produce reactive oxygen species and activate p38 MAPK
Experimental & Molecular Medicine
; : 101-110, 2011.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-186263
Responsible library:
WPRO
ABSTRACT
Previously, we reported that CD40-induced production of reactive oxygen species (ROS) by NADPH oxidase requires the TNF receptor-associated factor (TRAF) 3, as well as the activities of phosphatidylinositol 3-kinase (PI3K) and Rac1. Here we investigated the possible mechanisms of the production of ROS after CD40 ligation in B cells. We describe an alternative ROS production pathway that is triggered by CD40 ligation, involves 5-lipoxygenase (5-LO), and results in activation of p38 MAPK. Our studies in Raji human B lymphomas revealed that CD40-induced ROS production by 5-LO also requires the activities of PI3K and Rac1. In contrast to the NADPH oxidase pathway, however, TRAF molecules are not required for the CD40-induced ROS production by 5-LO. The association of CD40 with 5-LO is dependent on CD40 ligation in Raji B cells, and co-immunoprecipitation experiments using epitope-tagged proteins transiently expressed in human embryonic kidney 293T cells revealed the role of the regulatory subunit of PI3K, p85, in this association. Collectively, these data suggest a separate pathway for the CD40-induced ROS production in B cells and demonstrate that this pathway requires 5-LO via direct association of p85 with both CD40 and 5-LO.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Protein Binding
/
Arachidonate 5-Lipoxygenase
/
B-Lymphocytes
/
Signal Transduction
/
Reactive Oxygen Species
/
CD40 Antigens
/
Phosphatidylinositol 3-Kinases
/
Rac GTP-Binding Proteins
/
CD40 Ligand
/
Cell Line, Tumor
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2011
Document type:
Article