Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase during apoptosis.
The Fas system has been extensively investigated as a model of apoptosis and the caspase cascade has been shown to be a characteristic mechanism of signaling of apoptosis. We have identified and purified a kinase that was activated after the stimulation of Fas on human thymoma-derived HPB-ALL cells. Partial amino acid sequencing of the purified kinase revealed it to be MST/Krs, member of the yeast STE20 family of protein kinases. MST/Krs was activated by proteolytic cleavage and proteolytic activation was blocked by the caspase inhibitor, Z-VAD-FK. A mutant MST with Asp-->Asn replacement at a putative caspase cleavage site was resistant to either the proteolytic cleavage or the activation of the kinase activity. These findings suggest that proteolytic activation is one activation mechanism of MST and plays a role in apoptosis.
Lee
K K
KK
Institute for Virus Research, Kyoto University, Japan.
Murakawa
M
M
Nishida
E
E
Tsubuki
S
S
Kawashima
S
S
Sakamaki
K
K
Yonehara
S
S
D000595:Amino Acid Sequence; D017209:Apoptosis; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D000090742:Serine-Threonine Kinase 3; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism; D000099317:Hippo Kinases
D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D000090742:Serine-Threonine Kinase 3; D019014:fas Receptor; C095566:STK4 protein, human; D000099317:Hippo Kinases; C097835:STK3 protein, human; C078754:STE20 protein, S cerevisiae