Otani H, Erdos M, Leonard W J
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1993 Oct 25;268(30):22733-6.
Apoptosis (programmed cell death) plays a critical role in many physiological processes, but the mechanism(s) which regulate apoptosis are poorly understood. We demonstrate that in a hematopoietic cell line, which can grow in either interleukin (IL)-2 or IL-3, both of these growth factors can increase bcl-2 mRNA levels and prevent apoptosis normally seen following growth factor withdrawal. Herbimycin A, a protein tyrosine kinase inhibitor, blocks the ability of IL-2 and IL-3 to up-regulate bcl-2 mRNA levels and induces apoptosis. Transfection of a bcl-2 expression vector not only prolongs survival following growth factor withdrawal but also confers resistance to the effect of herbimycin A. We conclude that herbimycin A-sensitive protein tyrosine kinases are involved in the regulation of apoptosis and bcl-2 expression, but these protein tyrosine kinases appear not to be required for the action of Bcl-2 since Bcl-2 can exert its growth survival effect even in the presence of herbimycin A.
细胞凋亡（程序性细胞死亡）在许多生理过程中起着关键作用，但调节细胞凋亡的机制仍知之甚少。我们证明，在一种造血细胞系中，该细胞系可以在白细胞介素（IL）-2或IL-3中生长，这两种生长因子都可以增加bcl-2 mRNA水平，并防止在生长因子撤除后通常出现的细胞凋亡。蛋白酪氨酸激酶抑制剂赫曲霉素A可阻断IL-2和IL-3上调bcl-2 mRNA水平的能力，并诱导细胞凋亡。转染bcl-2表达载体不仅能延长生长因子撤除后的存活时间，还能赋予对赫曲霉素A作用的抗性。我们得出结论，对赫曲霉素A敏感的蛋白酪氨酸激酶参与细胞凋亡和bcl-2表达的调节，但这些蛋白酪氨酸激酶似乎不是Bcl-2发挥作用所必需的，因为即使在存在赫曲霉素A的情况下，Bcl-2也能发挥其生长存活效应。
