OVEREXPRESSION OF PROTEIN-KINASE-C ISOFORM-EPSILON BUT NOT ISOFORM-DELTA IN HUMAN INTERLEUKIN-3-DEPENDENT CELLS SUPPRESSES APOPTOSIS AND INDUCES BCL-2 EXPRESSION

Hematopoietic progenitor cells die by apoptosis after removal of the a ppropriate colony-stimulating factor (CSF). Recent pharmacologic data have implicated protein kinase C (PKC) in the suppression of apoptosis in interleukin-3 (IL-3) and granulocyte-macrophage (GM)-CSF-dependent human myeloid cells. Because IL-3 and GM-CSF induce increases in diac ylglycerol without mobilizing intracellular Ca++, it seemed that one o f the novel Ca++ independent isoforms of PKC was involved. We report h ere that overexpression of PKC epsilon in factor-dependent human TF-1 cells extends cell survival in the absence of cytokine. Overexpression of PKC delta does not have this effect. By 72 to 96 hours after cytok ine withdrawal, the PKC epsilon transfectants remain distributed in al l phases of the cell cycle, as shown by fluorescence-activated cell so rting (FAGS) analysis, while little intact cellular DNA is detectable in vector or PKC delta transfectants. PKC epsilon induces bcl-2 protei n expression fivefold to sixfold over the levels in empty vector trans fectants, whereas the levels in PKC delta transfectants are similar to those in vector controls. (C) 1998 by The American Society of Hematol ogy.