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 hema topoietic factors in increasing the colony formation of hematopoietic progenitor cells. We have shown that interleukin-3 (IL-3)-dependent pr oliferation of NFS-60 cells is associated with the induction of a spec ific 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 proliferat ive potential of NFS-60 cells in response to SCF is reflected in an in creased induction of the CaM-BP68. We observed that SCF alone has a li mited 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 I L-3-dependent induction of CaM-BP68 in the presence of SCF coincided w ith a corresponding increase in thymidine kinase activity, whose expre ssion is linked to G(1)/S transition of the cells. At low concentratio ns SCF caused a synergistic increase in IL-3-dependent induction of bo th CaM-BP68 and thymidine kinase activity. In contrast to the changes in CaM-BP68 and thymidine kinase activity, no significant changes in D NA polymerase alpha were observed in factor-deprived NFS-60 cells in r esponse to IL-3 and/or SCF. These observations suggest an increased ex pression of CaM-BP68 and thymidine kinase are associated with the syne rgistic effect of SCF on factor-dependent proliferation of hematopoiet ic progenitor cells. (C) 1996 by The American Society of Hematology.