Tyrosine kinase(s) regulate apoptosis and bcl-2 expression in a growth factor-dependent cell line

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.