サイトカインによる細胞の増殖分化と細胞死のシグナル伝達

造血细胞的存活取决于细胞因子信号，并且细胞在细胞因子耗尽时经历凋亡。由于我们已经证明了细胞因子刺激激活的RAS对于预防细胞死亡是重要的，我们通过使用RAS突变体分析了RAS下游的信号。我们发现，RAF/MAP激酶和由RAS激活的PI 3激酶都参与抑制细胞死亡。在没有细胞因子的情况下，半胱天冬酶-3被激活并参与诱导细胞死亡。此外，由于我们以前分离出的肿瘤抑制素M（OSM）作为一个精氨酸诱导的基因，我们寻找其生物活性。OSM被发现在AGM区域表达，并且显示出对造血细胞以及 ** 上皮细胞的发育具有深远的影响，可能作用于它们共同的前体细胞成血管细胞。利用AGM区的体外培养系统，研究了c-myb和AML在造血中的作用。OSM也被发现是发育中的支持细胞的生长因子。OSM受体的分子结构通过克隆受体cDNA来阐明。

Survival of hematopoietic cells depends on cytokine signals and cells undergo apoptosis upon cytokine depletion. As we have already demonstrated that RAS activated by cytokine stimulation is important for prevention of cell death, we analyzed signals downstream of RAS by using RAS mutants. We found that both RAF/MAP kinase and PI3 kinase activated by RAS are involved in suppression of cell death. In the absence of cytokines, caspase-3 is activated and is involved in induction of cell death. In addition, as we previously isolated Oncostatin M (OSM) as a cytokine-inducible gene, we searched for its biological activity. OSM was found to be expressed in the AGM region and was shown to have a profound effect on the development of hematopoietic cells as well as **dothelial cells, possibly acting on their common precursor cells, hemangioblasts. Using the in vitro culture system of the AGM region, role of c-myb and AML in hematopoiesis was studied. OSM was also found to be a growth factor of developing sertoli cells. The molecular structure of the OSM receptor was elucidated by cloning of the receptor cDNA.