Modification of oscillatory behaviour of protein tyrosine kinase and phosphatase during all-trans retinoic acid-induced differentiation of leukaemic cells

Granulocytic maturation of human acute promyelocytic leukaemic (HL-60) cells was induced using all-trans retinoic acid (ATRA). Time-dependent changes in the enzyme activities of protein tyrosine phosphatase (PTP) and protein tyrosine kinase (PTK), and the total extractable protein content were monitored in proliferating and differentiating cells. The existence of periodicity was demonstrated clearly in both PTP and PTK enzyme activities and in the amount of protein extracted from the cells. Following ATRA treatment, differentiation-induced changes in rhythmic characteristics such as period and amplitude were evident. A noticeable effect was that of ATRA on the enzyme activity of PTP, for which four distinct patterns of oscillatory behaviour were identified. This study examines these changes, in an attempt to gain insight into the role which biochemical oscillators may play in the regulation of molecular control mechanisms.