title: Sustained expression of the pim-1 kinase is specifically induced in myeloid cells by cytokines whose receptors are structurally related.
abstract: We have examined the effects of myeloid growth factors on expression of the pim-1 kinase protein in human and murine myeloid cells. pim-1 protein was identified in K562 cells by immunoblotting as a 33 kDa protein. In the human factor-dependent myeloid leukemia cell line M07E, pim-1 protein was induced by interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF), with maximum expression by 4 h. Expression continued for the duration of growth factor exposure, but declined rapidly when cytokines were removed. GM-CSF induced pim-1 protein in a dose-dependent manner, with expression being proportional to the proliferative effect of the cytokine. To examine the specificity of pim-1 protein induction, we compared pim-1 protein levels in myeloid cells which demonstrated different GM-CSF response phenotypes. We also examined the effects on pim-1 protein expression of different growth factors which induced similar response phenotypes. GM-CSF induced pim-1 protein in several myeloid cell lines, most of which demonstrated a proliferative response, but did not induce pim-1 protein expression in neutrophils or monocytic cells. In contrast, the murine cell line Mac-11 expressed pim-1 message in response to IL-3 and GM-CSF, but not in response to bryostatin or M-CSF, which were equivalent mitogens. In human U937 myeloid cells sustained expression of pim-1 protein was induced by GM-CSF, G-CSF and IL-6, but not by bryostatin. Expression of the pim-1 kinase protein in response to myeloid cytokines depends on both the nature of the growth factor and the response phenotype. The pim-1 kinase may be an important intermediate in transmembrane signaling or response phenotype induced by IL-3, GM-CSF and other cytokines whose receptors are structurally similar. Its constitutive expression in some myeloid leukemia cell lines suggests activation of signal cascades utilized by myeloid growth factors.
authors.affiliation: Department of Medicine, University of Washington, Seattle.
authors.forename: M
authors.initials: M
authors.lastname: Lilly
authors.forename: T
authors.initials: T
authors.lastname: Le
authors.forename: P
authors.initials: P
authors.lastname: Holland
authors.forename: S L
authors.initials: SL
authors.lastname: Hendrickson
mesh_terms: D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051573:Proto-Oncogene Proteins c-pim-1; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C496634:PIM1 protein, human; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1