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 inhibit the growth factor-induced signal transduction pathway at the post-receptor level. In this report, we examined the effect of staurosporine on the constitutive expression of tumor necrosis factor (TNF) receptors in K562, a human erythroblastoid leukemic cell line. Exposure of these cells to staurosporine enhanced cell surface expression of TNF receptors by almost 7-fold in a dose- and time-dependent fashion. Maximum induction occurred at a concentration of 20 nM of the agent for 16 h at 37 degrees C. Induction of the TNF receptor was found to be temperature 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 human cells of both epithelial (primarily p60 receptors) and myeloid (mainly p80 receptor) origin.