B cell receptor-mediated Syk-independent activation of phosphatidylinositol 3-kinase, Ras, and mitogen-activated protein kinase pathways.
The Syk tyrosine kinase is a key molecule in the development of the B cell lineage and the activation of B lymphocytes after Ag recognition by the B cell Ag receptor (BCR). Several genetic studies with chicken B cells have reported that the recruitment of Syk by BCR is essential for activation of a cascade of signaling molecules including phosphatidylinositol 3-kinase, mitogen-activated protein kinases, Ras signaling pathways, phospholipase C-gamma2 activation, and calcium mobilization. The identification of a Syk-deficient mouse IIA1.6/A20 B cell line provided us the opportunity to investigate Syk-mediated signaling in mouse. Surprisingly, phosphatidylinositol 3-kinase, Ras, and mitogen-activated protein kinases were activated upon BCR cross-linking in these Syk-deficient mouse B cells, whereas, as expected from results obtained in chicken B cells, phospholipase C-gamma2 activation and calcium mobilization were impaired as well as the NF-kappaB pathway. These results indicate that BCR signaling is not strictly dependent on Syk expression in mouse IIA1.6/A20 B cells. Thus, B lymphocyte activation may be initiated by Syk-dependent and Syk-independent signaling cascades.
Yokozeki
Takeaki
T
Institut National de la Santé et de la Recherche Médicale Unité 520, Institut Curie, Paris, France.
Adler
Kristin
K
Lankar
Danielle
D
Bonnerot
Christian
C
D000595:Amino Acid Sequence; D000818:Animals; D018941:Antigens, CD19 / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D004789:Enzyme Activation / Q000502:physiology; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D018631:ras Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology
D018941:Antigens, CD19; D004792:Enzyme Precursors; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D018631:ras Proteins; D002118:Calcium