Long-term changes in tyrosine phosphorylation of the abundant nuclear proteins during granulocytic differentiation of HL-60 cells

The two-dimensional electrophoretic patterns of nuclear proteins and their tyrosine phosphorylation were compared for HL-60 cells before and after dif ferentiation induction to granulocytes by dimethyl sulfoxide, all-trans ret inoic acid and N-6,O-2-dibutyryl adenosine 3':5'-cyclic monophosphate. Rega rdless of the inducer used, some nuclear proteins, which are tyrosine-phosp horylated in proliferating HL-60 cells, undergo gradual dephosphorylation 1 2-72 h after induction of differentiation, followed by drastic dephosphoryl ation during maturation to granulocytes. At least 13 nuclear proteins with a molecular mass of 35-110 kDa are dephosphorylated, and 6 nuclear proteins undergo tyrosine phosphorylation. Analysis of the nuclear proteins differe ntially extracted by salt and detergents indicates that changes in their ty rosine phosphorylation during the maturation stage of differentiating granu locytes occur mainly in proteins which are abundant in nucleoplasm, chromat in and residual nuclear structures. The abundance of these proteins, residi ng in the nuclear structures, and their long-term modification in phosphory lation during the maturation stages of differentiation strongly suggest tha t tyrosine phosphorylation of these proteins is involved in reorganization of the differentiating cell nucleus.