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

我们发现除莠霉素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，这两种分化系统被认为在其诱导机制上是完全不同的：胚胎癌细胞（F9）的内胚层分化和（MEL）细胞的终末红系分化。结果表明，有一个共同的步骤，在细胞内分化级联这是，直接或间接地，与磷酸化在特定的（酪氨酸）残基的细胞protein.A红细胞诱导活性检测无细胞提取物从MEL细胞已与二甲基亚砜或六亚甲基双乙酰胺孵育一段较长的时间。新检测到的活性明显不同于以前报道的分化诱导因子，似乎来自细胞质中的proeinacious因子。在提取物中的活性的外观的时间与细胞分化的承诺。该活性在分化缺陷MEL细胞系中不被诱导，并且该活性的诱导被MEL细胞分化的特异性抑制剂PMA抑制。

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.