Intranuclear translocation of phospholipase C beta 2 during HL-60 myeloid differentiation

Phospholipases C (PLC) beta 3, gamma 1, and gamma 2 were detected in nuclei of HL-60 promyelocitic leukaemia cells. When HL-60 cells undergo terminal myeloid differentiation in the presence of ATRA, the beta 2 isoform appeared inside nuclei and was up-regulated until 72 hours of ATRA treatment. The beta 3 isozyme was also increased until 72 hours and both isoforms lowered their intranuclear amount at 96 hours and following days of treatment, By contrast PLC gamma 1 and gamma 2 progressively increased in the nucleus during granulocytic differentiation even after 72 hours of treatment, Terminal differentiation was characterised by the expression of high levels of PLC gamma 1 and gamma 2 and by low levels of PLC beta 2 and beta 3 in the nucleus. PIP2 and PIP hydrolysis paralleled the prevalence of the beta or gamma subfamily, respectively. Moreover, at all the examined times no changes of PLCs in the whole cell were detectable, indicating a de novo nuclear translocation of the beta 2 and an increased accumulation of beta 3, gamma 1, and gamma 2 isoforms. Thus, the intranuclear presence, expression, and activity of PLC isozymes, which are modulated during differentiation of HL-60 cells, implicate a role for nuclear phosphoinositide signalling in the process of cell maturation. In particular the nuclear translocation of PLC beta 2 candidates this PLC as a key enzyme in the granulocytic differentiative commitment of HL-60 cells. (C) 1997 Academic Press.