title: Nonredundant roles of Src-family kinases and Syk in the initiation of B-cell antigen receptor signaling.
abstract: When a BCR on a mature B cell is engaged by its ligand, the cell becomes activated, and the Ab-mediated immune response can be triggered. The initiation of BCR signaling is orchestrated by kinases of the Src and Syk families. However, the proximal BCR-induced phosphorylation remains incompletely understood. According to a model of sequential activation of kinases, Syk acts downstream of Src family kinases (SFKs). In addition, signaling independent of SFKs and initiated by Syk has been proposed. Both hypotheses lack sufficient evidence from relevant B cell models, mainly because of the redundancy of Src family members and the importance of BCR signaling for B cell development. We addressed this issue by analyzing controlled BCR triggering ex vivo on primary murine B cells and on murine and chicken B cell lines. Chemical and Csk-based genetic inhibitor treatments revealed that SFKs are required for signal initiation and Syk activation. In addition, ligand and anti-BCR Ab-induced signaling differ in their sensitivity to the inhibition of SFKs.
authors: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic.
authors: Ondrej
authors: O
authors: Stepanek
authors: Peter
authors: P
authors: Draber
authors: Ales
authors: A
authors: Drobek
authors: Vaclav
authors: V
authors: Horejsi
authors: Tomas
authors: T
authors: Brdicka
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002645:Chickens; D004789:Enzyme Activation / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D054420:Pre-B Cell Receptors / Q000378:metabolism / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases