Studies of the differentiation of promyelocytic cells by phorbol ester. I. Induction of discrete membrane proteins characteristic of monocytes and expression of motility functions in HL-60 cells following differentiation by phorbol ester.

Cells of the promyelocytic leukemia line, HL-60, differentiate into macrophage-like cells in response to phorbol ester. We report that this effect is associated with induction of spontaneous motility and a modest expression of chemotactic responsiveness to a formylated peptide. Using two-dimensional gel electrophoresis we demonstrate that the differentiation of HL-60 cells is associated with a differential effect on membrane vs. cytosol proteins. Changes in the cytosol characteristically involved reduction of synthesis of specific proteins. Changes in the membrane were mainly associated with either enhancement or de novo synthesis of discrete proteins. The hallmark of HL-60 cell differentiation appeared to be distinctive induction of a membrane-bound group of six proteins (pI approximately equal to 5, 45-70 kDa) and the de novo induction of a membrane protein indicated as m10 (pI approximately equal to 7, 28 kDa). These discrete membrane proteins were found to be very prominently synthesized by human cultured monocytes, but virtually absent in lymphocytes. It is proposed that our ability to detect synthesis of proteins characteristic of different states of cellular differentiation will permit detailed studies of the biochemical changes which constitute this process. Definition of the role of these proteins and the mechanism regulating their synthesis will help to elucidate the biochemical basis of monocyte differentiation.