Stem cell factor enhances interleukin-3 dependent induction of 68-kD calmodulin-binding protein and thymidine kinase activity in NFS-60 cells.
Stem cell factor (SCF) is known to act synergistically with other hematopoietic factors in increasing the colony formation of hematopoietic progenitor cells. We have shown that interleukin-3 (IL-3)-dependent proliferation of NFS-60 cells is associated with the induction of a specific calmodulin-binding protein of about 68 kD (CaM-BP68). To evaluate the relationship between proliferative stimulation and the induction of CaM-BP68 by cytokines, we examined whether the increased proliferative potential of NFS-60 cells in response to SCF is reflected in an increased induction of the CaM-BP68. We observed that SCF alone has a limited effect on proliferative stimulation and on the induction of CaM-BP68 in factor-deprived NFS-60 cells. However, when combined with IL-3, granulocyte colony-stimulating factor (G-CSF), or IL-6, it caused a significant increase in cytokine-dependent proliferative stimulation, as well as in the induction of CaM-BP68. Furthermore, an increase in IL-3-dependent induction of CaM-BP68 in the presence of SCF coincided with a corresponding increase in thymidine kinase activity, whose expression is linked to G1/S transition of the cells. At low concentrations SCF caused a synergistic increase in IL-3-dependent induction of both CaM-BP68 and thymidine kinase activity. In contrast to the changes in CaM-BP68 and thymidine kinase activity, no significant changes in DNA polymerase alpha were observed in factor-deprived NFS-60 cells in response to IL-3 and/or SCF. These observations suggest an increased expression of CaM-BP68 and thymidine kinase are associated with the synergistic effect of SCF on factor-dependent proliferation of hematopoietic progenitor cells.
Reddy
G P
GP
Department of Cell Biology, University of Massachusetts, Medical Center, Worcester, MA 01605, USA.
Quesenberry
P J
PJ
D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004257:DNA Polymerase II / Q000032:analysis; D004357:Drug Synergism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology; D019089:Stem Cell Factor / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D002148:Calmodulin-Binding Proteins; D016895:Culture Media, Serum-Free; D007377:Interleukin-3; D015850:Interleukin-6; D009363:Neoplasm Proteins; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013937:Thymidine Kinase; D004257:DNA Polymerase II