|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1989 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Our previous report (Okazaki et al J. Cell. Physiol. 131 : 50, 1987) demonstrated that HL-60 cells treated with 1 alpha 25 (OH) _2D_3 in magnesium deficient medium were committed to differentiate but did not express differentiation related phenotypes. In the present study we demonstrated that magnesium deprivation blocks the process of differentiation before the induction of phenotypic mRNA such as that of lysozyme, suggesting the process of differentiation can be divided into two steps, i. e. a step before the induction of a phenotypic messenger RNA, and a step after that. In the present study we referied the former step as a commitment step (CS) and the latter as a phenotypic expression step (PS). We studied the effect of protein kinase A (PKA) and protein kinase C (PKC) modulators in each step. The results indicated that dbc-AMP, folskolin enhanced both steps, but H-8 inhibited them. On the other hand OAG, TPA enhanced CS, but inhibited PS. Staurospor in and H-7 inhibited CS and enhanced PS. These results indicate that PKA acts as a positive regulatory signal, and that PKC has a dual action in the process of differentiation, i. e. as a positive regulatory signal in CS, and as a negative one in' PS. Recently we showed that in K-562 cell differentiation into erythroid lineage, PKA serves as a negative signal in both steps and PKC acts dually, namely as a negative signal in CS and positive one in PS (Yumoto et al J. Cell. Physiol. 143 : 243, 1990). Interestingly the functions of PKA and PKC in the process of these two cell lines appear to be reversed, although PKC may act dually in both cell lines.