title: K252a, a potent inhibitor of protein kinases, promotes the transition of Dictyostelium cells from growth to differentiation.
abstract: Cell differentiation and proliferation are mutually exclusive processes in many cases. The transition of starving Dictyostelium cells from growth to differentiation phase has been shown to occur at a particular position (putative shift point; PS-point) in the cell cycle of D. discoideum Ax-2. The significance of phosphorylation states of proteins such as 101 kDa, 90 kDa, and 32 kDa phosphoproteins has been argued, particularly around the PS-point. In this study we examined effects of the protein kinase inhibitors and activators on the transition of Ax-2 cells from growth to differentiation. K252a, a potent inhibitor of protein kinases, inhibited growth possibly through the blockage of pinocytotic activity of cells, and promoted the progress of development after starvation when applied to Ax-2 cells at the growth phase. Such a K252a-effect was most pronouncedly exhibited on the cells located near the PS-point. Unexpectedly, however, the development of starved cells was found to be considerably delayed by staurosporine bearing a structural and functional resemblance to K252a when it was applied during the growth phase. Pulse-labelings of growing Ax-2 cells with inorganic 32P (32Pi) showed that K252a induces the disappearance of a 48 kDa phosphoprotein and the appearance of a 50 kDa phosphoprotein, specifically in the cells located around the PS-point. Phosphorylation of 32 kDa and 24 kDa proteins was also inhibited by K252a, but this inhibition was not necessarily specific to the K252a-treatment and occurred independently of the cell-cycle phases. The possible significance of these results is discussed in relation to a breakaway of cells from proliferation to differentiation at the PS-point.
authors.affiliation: Biological Institute, Faculty of Science, Tohoku University, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004023:Dictyostelium / Q000166:cytology / Q000187:drug effects*; D026121:Indole Alkaloids; D010873:Pinocytosis / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D015398:Signal Transduction; D019311:Staurosporine
chemical_list: D000470:Alkaloids; D002227:Carbazoles; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; C049985:staurosporine aglycone; D019311:Staurosporine