CHANGES IN PROTEIN-KINASE ACTIVITY WITHIN 30 MIN OF INDUCED-DIFFERENTIATION IN FRIEND-ERYTHROLEUKEMIA CELLS

Induction of maturation in Friend erythroleukemia cells is accompanied by a programmed cessation in cell proliferation and a concomitant inc rease in hemoglobin production. To investigate the role of protein kin ase activity in the initiation of Friend erythroleukemia cell differen tiation, autoradiographs of one-dimensional, nondenaturing gels were p repared from Friend erythroleukemia cells either untreated or preincub ated with dimethyl sulfoxide (DMSO) or aphidicolin for a 30-min period . Extracts were treated with cAMP or cGMP prior to electrophoresis and assayed for protein kinase activity in the presence of endogenous or exogenously added histone substrates. The data demonstrated difference s in protein kinase activity following exposure of Friend erythroleuke mia cells to either DMSO or aphidicolin for 30 min. These changes in e nzyme activity varied with the treatment of the cells and the substrat e used. Two sets of protein kinases, one responsive to cAMP and the ot her responsive to cGMP, were activated in control cultures. A differen t cAMP-responsive enzyme was active only in differentiating cells. Ano ther protein kinase, activated by cGMP, was associated with both DMSO and aphidicolin treatment. All of these protein kinases had a histone substrate preference. One noncyclic nucleotide activated protein kinas e phosphorylating endogenous substrates was associated only with DMSO- induced cells. These findings suggest a multifaceted role for protein kinases early in the maturation of Friend erythroleukemia cells.