Alterations in insulin receptor kinase activity during differentiation of HL-60 cells

Abstract

Differentiation of the human promyelocytic leukemia cell line HL-60 into monocytes or macrophages is associated with increased expression of cell surface insulin receptors, while differentiation of these cells into granulocytes is associated with receptor loss. Here we demonstrate that differentiation of HL-60 cells into monocytes or granulocytes induced by 1;25(OH) 2vitD 3 or Bt 2cAMP, respectively, has no major effect on the specific activity of the insulin receptor kinase (IRK). By contrast, when HL-60 cells are incubated with a combination of 1;25(Oh) 2vitD 3 and Bt 2cAMP, their differentiation into adherent macrophages-like cells is accompanied by a 505 reduction in the specific activity of IRK. These findings suggest that acquisition or loss of insulin receptors during differentiation of HL-60 involves selective alterations in the functional aspects of these receptors. Our results also implicate the generation of specific regulatory signals that inhibit IRK activity when HL-60 cells are stimulated with a combination of 1;25(OH) 2vitD 3 and Bt 2cAMP.