Fukumoto H, Matsui Y, Obinata M
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Development. 1989 Jan;105(1):109-14. doi: 10.1242/dev.105.1.109.
Erythropoietin is a well-known erythroid differentiation and growth factor, but the mechanism of its action is not well understood. In this work, we have examined its mechanism of action on the erythropoietin-responsive murine erythroleukemia cells (TSA8). TSA8 cells become responsive to erythropoietin after induction with DMSO. Stimulatory effects on erythropoietin response are observed with the addition of compounds affecting the cAMP level such as forskolin, phosphodiesterase inhibitor and cholera toxin only in the presence of erythropoietin. cAMP analogues themselves show no stimulatory effect on TSA8 cells, nor does erythropoietin increase cAMP level in the cells. Thus, it is suggested that cAMP does not act as a direct second messenger for signal transduction through erythropoietin receptors, but as a stimulator of the erythropoietin receptor pathway and/or as a second messenger in combination with the receptor pathway. The mechanism for acquisition of responsiveness to growth and differentiation factors of progenitor cells is discussed.
促红细胞生成素是一种众所周知的红细胞分化和生长因子，但其作用机制尚未完全明确。在本研究中，我们研究了其对促红细胞生成素反应性小鼠红白血病细胞（TSA8）的作用机制。TSA8细胞在用二甲基亚砜诱导后对促红细胞生成素产生反应。仅在存在促红细胞生成素的情况下，添加影响环磷酸腺苷（cAMP）水平的化合物，如福斯可林、磷酸二酯酶抑制剂和霍乱毒素，可观察到对促红细胞生成素反应的刺激作用。cAMP类似物本身对TSA8细胞无刺激作用，促红细胞生成素也不会增加细胞内的cAMP水平。因此，有人提出cAMP并非作为通过促红细胞生成素受体进行信号转导的直接第二信使，而是作为促红细胞生成素受体途径的刺激剂和/或与受体途径结合的第二信使。本文还讨论了祖细胞获得对生长和分化因子反应性的机制。
