Sustained expression of the pim-1 kinase is specifically induced in myeloid cells by cytokines whose receptors are structurally related.

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.