Bryostatin I Activates Protein Kinase C and Induces Monocytic Differentiation of HL-60 Cells

Phorbol esters induce the human HL-60 promyelocytic cell line to differentiate along a monocytic pathway. This induction of differentiation may involve phorbol esterinduced activation of the phospholipidand calcium-dependent protein kinase C. Bryostatin 1 #{149} a macrocyclic lactone. has been shown to compete with phorbol esters for binding to protein kinase C. We have confirmed that bryostatin 1 translocates activity of protein kinase C from the cytosolic to membrane fractions of Hl-60 cells. The present results also demonstrate that bryostatin 1 (10 nmol/l) induces monocytic differentiation of Hl-60 cells as determined by adherence, growth inhibition. appearance of monocyte cell surface antigens. and a-naphthyl acetate esterase staining. Furthermore, bryostatin 1 (10 nmol/l) downregulated c-