Studies on intracellular factors involved in cellular differentiation of mouse and human cells.

我们发现herbimycin A是一种有效的诱导剂，能够在两种典型的小鼠体外分化系统中触发分化，这两种系统的诱导机制被认为是完全不同的：胚胎癌（F9）细胞的内胚层分化和MEL细胞的终末红细胞分化。结果表明，在细胞内分化级联中存在一个共同的步骤，该步骤直接或间接地与细胞蛋白特定（酪氨酸）残基的磷酸化有关。用二甲亚砜或六亚甲双乙酰胺长时间孵育MEL细胞的无细胞提取物，检测到红细胞诱导活性。新检测到的活性与先前报道的分化诱导因子明显不同，似乎来自细胞质中的特异因子。提取物中出现活性的时间与细胞分化的时间一致。在分化缺陷的MEL细胞系中，该活性未被诱导，其诱导活性是由MEL细胞分化特异性抑制剂PMA介导的。

We have found that herbimycin A is an effective inducing agent capable of triggering differentiation in two typical mouse in vitro differentiation systems, which have been considered to be quite different in their mechanism of induction: endoderm differentiation of embryonal carcinoma (F9) cells and terminal erythroid differentiation of (MEL) cells. The results suggest that there is a common step in the intracellular differentiation cascade which is, directly or indirectly, associated with phosphorylation at specific (tyrosine) residues of cellular proteins.An erythroid-inducing activity was detected in cell-free extracts from MEL cells which had been incubated with dimethyl sulfoxide or hexamehylenebisacetamide for a prolonged period of time. The newly detected activity was apparently different from the previously reported differentiation-inducing factors and seemed to be derived from a proeinacious factor in the cytoplasm. The timing of the appearance of the activity in the extracts coincided with that of cellular commitment to differentiation. The activity was not induced in a differentiation defective MEL cell line and the induction of the activity was inhabited by PMA, a specific inhibitor for MEL cell differentiation.