herbimycin has been researched along with Precursor-B-Cell-Lymphoblastic-Leukemia-Lymphoma* in 2 studies
2 other study(ies) available for herbimycin and Precursor-B-Cell-Lymphoblastic-Leukemia-Lymphoma
Article | Year |
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The role of Aktand RAFTK in beta1 integrin mediated survival of precursor B-acute lymphoblastic leukemia cells.
In this study, we report that the related adhesion focal tyrosine kinase RAFTK, is an upstream kinase in beta1 integrin mediated activation of Akt. Stimulation through beta1 integrins by fibronectin reversed apoptosis induced by adriamycin. Inhibitors of phosphatidylinositol 3-kinase (PI3 kinase)/Akt (LY 294002), tyrosine kinases (Herbimycin-A) and the cytotoxic agent adriamycin induced apoptosis of REH cells. beta1 integrin ligation induced activation of Akt, and tyrosine phosphorylation of RAFTK and FAK, but not SYK in REH cells. This suggested that RAFTK and FAK activation might be linked to Akt activation. Evidence that RAFTK is a modulator of Akt came from phorbol myristic acetate (PMA) stimulation. RAFTK and Akt were activated but FAK was not. Using fibroblasts from FAK -/- mice, which express high levels of RAFTK, fibronectin plating enhanced Akt activation. Pretreatment of REH cells with a P13 kinase/Akt inhibitor LY 294002 did not inhibit RAFTK tyrosine phosphorylation showing that RAFTK is upstream of P13k/Akt. Further evidence for a link between RAFTK tyrosine phosphorylation and Akt activation was the observation that the p85 subunit of P13 kinase associated with RAFTK following integrin ligation in REH cells. These results suggest that RAFTK plays an anti-apoptotic role through the activation of Akt. Topics: Benzoquinones; Cell Survival; Doxorubicin; Enzyme Activation; Fibronectins; Focal Adhesion Kinase 2; Humans; Integrin beta1; Lactams, Macrocyclic; Phosphatidylinositol 3-Kinases; Phosphorylation; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Quinones; Rifabutin; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured | 2002 |
Role of tyrosine phosphorylation in radiation-induced cell cycle-arrest of leukemic B-cell precursors at the G2-M transition checkpoint.
Here we provide experimental evidence that ionizing radiation induces inhibitory tyrosine phosphorylation of the p34cdc2 kinase in human leukemic B-cell precursors. Herbimycin A markedly reduced tyrosine phosphorylation of p34cdc2 in irradiated leukemic B-cell precursors, thereby preventing radiation-induced cell cycle arrest at the G2-M transition checkpoint. Thus, tyrosine phosphorylation is directly responsible for the inactivation of p34cdc2 in irradiated human leukemic B-cell precursors and activation of protein tyrosine kinases is a proximal and mandatory step in radiation-induced G2-arrest arrest at the G2-M checkpoint. Human WEE1 kinase isolated from unirradiated or irradiated leukemic B-cell precursors had minimal tyrosine kinase activity towards p34cdc2. We detected no increase of human WEE1 kinase activity after radiation of leukemic B-cell precursors, as measured by (a) autophosphorylation, (b) tyrosine phosphorylation of a synthetic peptide derived from the p34cdc2 amino-terminal region or (c) recombinant human p34cdc2-cyclin B complex. Thus the signaling pathway leading to inhibitory tyrosine phosphorylation of p34cdc2 and G2-arrest in irradiated human leukemic B-cell precursors functions independent of p49 WEE1 HU and enzymes which augment the tyrosine kinase activity of p49 WEE 1HU. Topics: B-Lymphocytes; Benzoquinones; CDC2 Protein Kinase; Cell Cycle Proteins; Enzyme Activation; G2 Phase; Hematopoietic Stem Cells; Humans; Lactams, Macrocyclic; Macromolecular Substances; Maturation-Promoting Factor; Neoplasm Proteins; Neoplastic Stem Cells; Nuclear Proteins; Peptide Fragments; Phosphorylation; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Quinones; Recombinant Fusion Proteins; Rifabutin; Tumor Cells, Cultured; Tyrosine | 1996 |