Growth factor stimulation of hematopoietic cells leads to membrane translocation of AKT1 protein kinase.
AKT1 is the human homolog of the v-akt oncogene. AKT1 has two distinct protein domains, one serine/threonine kinase domain and one pleckstrin homology (PH) domain. We studied the expression and activity of AKT1 in hematopoietic cell lines. The expression of AKT1 was constitutive in hematopoietic cells of various stages of development. In the growth factor dependent MO7e cells, serum and growth factor starvation resulted in an early 50% fall in activity which was maintained over 24 h. Treatment of cells which growth factors or agents which induce differentiation activated AKT1. The subcellular localization of AKT1 in MO7e cells was altered as it was activated. High AKT1 kinase activity was associated with membrane fractions in stimulated cells, in contrast to the much lower AKT1 activity in membranes of cells starved of serum and growth factor for 1 h. These results demonstrate AKT1 kinase activity and its regulation by extracellular signaling factors in vivo in hematopoietic cells, and suggest that the activation of AKT1 involves intracellular translocation of the kinase from cytosol to membrane.
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Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202, USA.
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D001692:Biological Transport; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000494:pharmacology; D012190:Retroviridae / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D017385:Sequence Homology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C494918:AKT1 protein, human; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt