H. Otani et al., TYROSINE KINASE(S) REGULATE APOPTOSIS AND BCL-2 EXPRESSION IN A GROWTH FACTOR-DEPENDENT CELL-LINE, The Journal of biological chemistry, 268(30), 1993, pp. 22733-22736
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.