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 physio logical processes, but the mechanism(s) which regulate apoptosis are p oorly understood. We demonstrate that in a hematopoietic cell line, wh ich can grow in either interleukin (IL)-2 or IL-3, both of these growt h factors can increase bcl-2 mRNA levels and prevent apoptosis normall y seen following growth factor withdrawal. Herbimycin A, a protein tyr osine kinase inhibitor, blocks the ability of IL-2 and IL-3 to up-regu late bcl-2 mRNA levels and induces apoptosis. Transfection of a bcl-2 expression vector not only prolongs survival following growth factor w ithdrawal but also confers resistance to the effect of herbimycin A. W e conclude that herbimycin A-sensitive protein tyrosine kinases are in volved in the regulation of apoptosis and bcl-2 expression, but these protein tyrosine kinases appear not to be required for the action of B cl-2 since Bcl-2 can exert its growth survival effect even in the pres ence of herbimycin A.