Patel H R, Choi H S, Sytkowski A J
New England Deaconess Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215.
J Biol Chem. 1992 Oct 25;267(30):21300-2.
Erythropoietin stimulation of erythroid cells induces a rapid increase in c-myc and decrease in c-myb mRNA levels. The signal pathway to c-myc requires activation of protein kinase C. We now report that erythropoietin down-regulates expression of c-myb via a discrete, serine/threonine-specific phosphatase-dependent pathway. The protein kinase C-blocker H7 completely prevents the c-myc response to erythropoietin, but has no effect on the c-myb response. In contrast, the phosphatase blocker okadaic acid prevents the c-myb response but not the c-myc response. This effect of okadaic acid on the c-myb response is concentration-dependent. Both the protein kinase C-dependent signal to c-myc and the phosphatase-dependent signal to c-myb regulate gene expression by a transcriptional arrest mechanism operative within the first intron of the respective protooncogenes. In contrast, the chemical inducer of differentiation, dimethyl sulfoxide, regulates expression of c-myc and c-myb without activation of these phosphatase- and kinase-dependent pathways.
促红细胞生成素对红系细胞的刺激可诱导c-myc迅速增加，c-myb mRNA水平降低。通向c-myc的信号通路需要蛋白激酶C的激活。我们现在报告，促红细胞生成素通过一条离散的、丝氨酸/苏氨酸特异性磷酸酶依赖性途径下调c-myb的表达。蛋白激酶C阻断剂H7完全阻止了c-myc对促红细胞生成素的反应，但对c-myb的反应没有影响。相反，磷酸酶阻断剂冈田酸阻止了c-myb的反应，但不影响c-myc的反应。冈田酸对c-myb反应的这种影响是浓度依赖性的。通向c-myc的蛋白激酶C依赖性信号和通向c-myb的磷酸酶依赖性信号都通过在各自原癌基因的第一个内含子内起作用的转录停滞机制来调节基因表达。相比之下，分化化学诱导剂二甲基亚砜在不激活这些磷酸酶和激酶依赖性途径的情况下调节c-myc和c-myb的表达。
