title: Dominant negative form of alpha4 inhibits the BCR crosslinking-induced phosphorylation of Bcl-xL and apoptosis in an immature B cell line WEHI-231.
abstract: We previously demonstrated that c-Jun N-terminal kinase (JNK) phosphorylates serine 62 of Bcl-xL to induce the degradation of Bcl-xL and apoptosis in WEHI-231 cells upon BCR crosslinking. In order to elucidate the regulatory mechanisms underlying the phosphorylation of Bcl-xL, we prepared an assay system in which JNK phosphorylated Bcl-xL in HEK293T cells. Consequently, we found that a signal transduction molecule, alpha4, enhanced the phosphorylation of Bcl-xL by JNK, while the co-expression of C-terminal alpha4 (220-340) diminished the phosphorylation of Bcl-xL induced by JNK. Furthermore, full-length alpha4 associated with both JNK and Bcl-xL, whereas C-terminal alpha4 (220-340) associated only with Bcl-xL, not JNK. In addition, WEHI-231 cells transfected with the cDNA of C-terminal alpha4 (220-340) exhibited decreased phosphorylation of Bcl-xL and stronger resistance to apoptosis induced by BCR crosslinking. These results indicate that alpha4 is an important regulatory molecule of apoptosis induced by BCR crosslinking in WEHI-231 cells and that C-terminal alpha4 (220-340) functions as a dominant negative form.
authors: Department of Immunology and Hematology, Graduate School of Health Sciences, Faculty of Life Sciences, Kumamoto University.
authors: Kano
authors: K
authors: Tanabe
authors: Seiji
authors: S
authors: Inui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D018832:Molecular Chaperones; D010766:Phosphorylation; D054448:Precursor Cells, B-Lymphoid / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D051562:Proto-Oncogene Proteins c-bcr / Q000502:physiology*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C494811:BCL2L1 protein, human; C490467:IGBP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D051020:bcl-X Protein; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr