Augmentation of retinoic acid‐induced granulocytic differentiation in HL‐60 leukemia cells by serine/threonine protein phosphatase inhibitors

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Abstract
To evaluate the involvement of protein phosphatases (PP) in differentiation of human myclogenous leukemia HL‐60 cells, we made use of potent inhibitors of PP1 and PP2A, calyculin‐A (CAL‐A) and okadaic acid (OKA). CAL‐A and OKA could augment all‐trans retinoic acid (ATRA)‐induced granulocytic differentiation, whereas the differentiation toward macrophage lineage by 12‐o‐tetradecanoylphorbol acetate (TPA) was unchanged in the presence of CAL‐A. CAL‐A augmented the phosphorylation or 18K, 23K and 30K proteins induced by ATRA. The PP1 and PP2A were identified and were present mainly in the cytosol of HL‐60 cells. These results suggest that either PP1 or PP2A or both may be involved in regulating granulocytic differentiation or HL‐60 cells.