title: Protein phosphatase 6 controls BCR-induced apoptosis of WEHI-231 cells by regulating ubiquitination of Bcl-xL.
abstract: Crosslinking BCR in the immature B cell line WEHI-231 causes apoptosis. We found that Bcl-xL was degraded by polyubiquitination upon BCR crosslinking and in this study explored the mechanism that controls the degradation of Bcl-xL. Ser(62) of Bcl-xL was phosphorylated by JNK to trigger polyubiquitination, and this was opposed by serine/threonine protein phosphatase 6 (PP6) that physically associated with Bcl-xL. We show BCR crosslinking decreased PP6 activity to allow Ser(62) phosphorylation of Bcl-xL. CD40 crosslinking rescues BCR-induced apoptosis, and we found PP6 associated with CD40 and PP6 activation in response to CD40. Our data suggest that PP6 activity is regulated to control apoptosis by modulating Ser(62) phosphorylation of Bcl-xL, which results in its polyubiquitination and degradation.
authors.affiliation: Department of Immunology and Hematology, Faculty of Life Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto 862-0976, Japan; and.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kajihara
authors.affiliation: Department of Immunology and Hematology, Faculty of Life Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto 862-0976, Japan; and.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Department of Immunology and Hematology, Faculty of Life Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto 862-0976, Japan; and.
authors.forename: Kano
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Department of Immunology and Hematology, Faculty of Life Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto 862-0976, Japan; and.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takemoto
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 862-0976, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 862-0976, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.affiliation: Department of Immunology and Hematology, Faculty of Life Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto 862-0976, Japan; and inui@kumamoto-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Inui
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000276:immunology*; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D059748:Proteolysis; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D054875:Ubiquitination / Q000235:genetics / Q000276:immunology*; D051020:bcl-X Protein / Q000235:genetics / Q000276:immunology*
chemical_list: C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D011947:Receptors, Antigen, B-Cell; D051020:bcl-X Protein; D048670:MAP Kinase Kinase 4; D010749:Phosphoprotein Phosphatases