PROTEOLYTIC ACTIVATION OF MST KRS, STE20-RELATED PROTEIN-KINASE, BY CASPASE DURING APOPTOSIS/

The Fas system has been extensively investigated as a model of apoptos is and the caspase cascade has been shown to be a characteristic mecha nism of signaling of apoptosis. We have identified and purified a kina se that was activated after the stimulation of Fas on human thymoma-de rived HPB-ALL cells. Partial amino acid sequencing of the purified kin ase revealed it to be MST/ Krs, member of the yeast STE20 family of pr otein kinases. MST/Krs was activated by proteolytic cleavage and prote olytic activation was blocked by the caspase inhibitor, Z-VAD-FK. A mu tant MST with Asp-->Asn replacement at a putative caspase cleavage sit e was resistant to either the proteolytic cleavage or the activation o f the kinase activity. These findings suggest that proteolytic activat ion is one activation mechanism of MST and plays a role in apoptosis.