Cd19-dependent activation of Akt kinase in B-lymphocytes.
CD19 is rapidly phosphorylated upon B-cell antigen receptor (BCR) cross-linking, leading to the recruitment of downstream signaling intermediates. A prominent feature of CD19 signaling is the binding and activation of phosphoinositide 3-kinase (P13K), which accounts for the majority of PI3K activity induced by BCR ligation. Recent findings have implicated activation of the serine/threonine kinase Akt as imparting survival signals in a PI3K-dependent fashion. Using CD19-deficient B-lymphoma cells and mouse splenic B-cells, we show that CD19 is necessary for efficient activation of Akt following cross-linking of surface immunoglobulin or Igbeta. In the absence of CD19, Akt kinase activity is reduced and transient. In addition, coligation of CD19 with surface immunoglobulin leads to augmented Akt activity in a dose-dependent manner. Thus, CD19 is a key regulator of Akt activity in B-cells; as such it may contribute to pre-BCR or BCR-mediated cell survival in vivo.
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Division of Biology and UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093-0322, USA.
Omori
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Rickert
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D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D018941:Antigens, CD19 / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D004789:Enzyme Activation; D014644:Genetic Variation; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018941:Antigens, CD19; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human