Inositide-modifying enzymes in differentiation of myeloid cells

摘要

Differentiation and response of neutrophils to inflammatory stimuli consist of a complex sequence of events including cytoskeleton remodelling and shape changes. While a number of studies performed with different approaches have indicated the involvement of PLC and PI 3-K pathways in a variety of chemoattractant-induced responses, the issue of whether these inositide-modifying enzymes play a role also in modulating the pheno-typical maturation process of inflammation cells has not been fully addressed. Recent work performed on myeloid cells demonstrated that the ATRA-induced gra-nulocytic maturation of the HL-60 promyelocytic cell line, a well studied model of neutrophil-like differentiation, is accompanied by the accumulation of specific iso-forms of PLC and PI 3-K. inside the nuclear compartment of differentiated cells. In particular, it has been found that the activity of PI 3-K, that appears to be essential for the differentiative process, is dependent on its Interaction with actin, in both cytoplasm and nuclear compartments of HL-60 cells. PI 3-K/actin association inside the nucleus is mediated by tyrosine phosphory-lated Vav, which may then be responsible of targeting PI 3-K to its nuclear matrix-associated intranuclear substrates. Stemming from the notion that the changes in cytoskeleton assembly are regulated by phosphoinosi-tides, we review the data concerning the intranuclear expression and activity of specific inositide-modifying enzymes during differentiation of tumoral myeloid precursors. The collected evidences suggest that changes of the intranuclear pool of phosphoinositides play key roles in the changes of the nucleoskeleton that characterize granulocytic maturation.