Open AccessOkadaic acid suppresses TPA‐induced differentiation by stimulating G 1 /S transition in human myeloblastic leukaemia ML‐1 cells
Author(s) -
Reinach P. S.,
Li T.,
Lu L.
Publication year - 2000
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1046/j.1365-2184.2000.00162.x
Subject(s) - okadaic acid , dephosphorylation , phosphorylation , retinoblastoma protein , protein kinase a , cell cycle , protein kinase c , kinase , biology , stimulation , microbiology and biotechnology , cellular differentiation , phosphatase , apoptosis , endocrinology , biochemistry , gene
The association between the phosphorylation status of the retinoblastoma protein, pRb and changes in cell cycle control caused by either protein kinase C (PKC) or protein kinase A (PKA) stimulation was evaluated in human myeloblastic leukaemia ML‐1 cells. TPA‐induced PKC activation resulted in dephosphorylation of pRb and subsequently induced ML‐1 differentiation based on morphological changes and CD14 expression. In the present study, we showed that inhibition of protein phosphatases (PP‐1 and PP‐2a) prevented the TPA‐induced differentiation in ML‐1 cells. Preinhibition of PP‐1 and PP‐2a activities with 1–100 nM okadaic acid dose‐dependently blunted the decrease in the phosphorylation status of pRb obtained with TPA and overrode cell cycle arrest. PKA stimulation with 8‐chlorophenylthio‐cAMP (100 µM) decreased cell proliferation by 65% and the distribution of cells in the G 1 phase significantly increased from 38% to 83% concomitant with a 34% decline in the number of cells present in the S phase. In addition, PKA stimulation significantly decreased the pRb phosphorylation status but did not elicit CD14 expression, indicating that cAMP‐induced dephosphorylation of pRb cannot by itself trigger differentiation in ML‐1 cells.