STAUROSPORINE-INDUCED THYMOCYTE APOPTOSIS IS INHIBITED BY HERBIMYCIN-A, A SPECIFIC INHIBITOR OF PROTEIN-TYROSINE KINASE

When mouse thymocytes were incubated with staurosporine at low doses ( 1-100 nM), increased tyrosine phosphorylation of proteins with a molec ular weight of 31-34 kD in the detergent-soluble fraction was observed , together with an increase in internucleosomal DNA fragmentation. Inc ubation with staurosporine for 6 h was enough to trigger and progress of apoptosis. Herbimycin A, a specific inhibitor of protein tyrosine k inases, and cycloheximide, an inhibitor of protein synthesis, reduced the amount of the phosphotyrosine proteins, this being followed by the inhibition of DNA fragmentation and cell death, suggesting a close re lationship between, protein tyrosine phosphorylation and the induction of apoptosis by staurosporine.