STAUROSPORINE INDUCES THE CELL-SURFACE EXPRESSION OF BOTH FORMS OF HUMAN TUMOR-NECROSIS-FACTOR RECEPTORS ON MYELOID AND EPITHELIAL-CELLS AND MODULATES LIGAND-INDUCED CELLULAR-RESPONSE

Staurosporine, an inhibitor of protein kinase C, is commonly used to i nhibit the growth factor-induced signal transduction pathway at the po st-receptor level. In this report, we examined the effect of staurospo rine on the constitutive expression of tumor necrosis factor (TNF) rec eptors in K562, a human erythroblastoid leukemic cell line. Exposure o f these cells to staurosporine enhanced cell surface expression of TNF receptors by almost 7-fold in a dose- and time-dependent fashion. Max imum induction occurred at a concentration of 20 nM of the agent for 1 6 h at 37 degrees C. Induction of the TNF receptor was found to be tem perature dependent. No induction was observed at 22 or at 4 degrees C, suggesting the role of cell metabolism. Scatchard analysis indicated an increase in receptor number without any change in receptor affinity . TNF receptors were induced by staurosporine on a wide variety of hum an cells of both epithelial (primarily p60 receptors) and myeloid (mai nly p80 receptor) origin.