title: Syk mediates BCR- and CD40-signaling integration during B cell activation.
abstract: CD40 is essential for optimal B cell activation. It has been shown that CD40 stimulation can augment BCR-induced B cell responses, but the molecular mechanism(s) by which CD40 regulates BCR signaling is poorly understood. In this report, we attempted to characterize the signaling synergy between BCR- and CD40-mediated pathways during B cell activation. We found that spleen tyrosine kinase (Syk) is involved in CD40 signaling, and is synergistically activated in B cells in response to BCR/CD40 costimulation. CD40 stimulation alone also activates B cell linker (BLNK), Bruton tyrosine kinase (Btk), and Vav-2 downstream of Syk, and significantly enhances BCR-induced formation of complex consisting of, Vav-2, Btk, BLNK, and phospholipase C-gamma2 (PLC-γ2) leading to activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase, Akt, and NF-κB required for optimal B cell activation. Therefore, our data suggest that CD40 can strengthen BCR-signaling pathway and quantitatively modify BCR signaling during B cell activation.
authors.affiliation: Section of Nephrology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., IL 60637, United States.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ying
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Li
authors.forename: Lifen
authors.initials: L
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019013:CD40 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D019013:CD40 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; C490565:Vav2 protein, mouse; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051966:Phospholipase C gamma