Prostate-derived Sterile 20-like Kinase 2 (PSK2) Regulates Apoptotic Morphology via C-Jun N-terminal Kinase and Rho Kinase-1

• Published in: The Journal of biological chemistry Vol. 281; no. 11; pp. 7317 - 7323
• Main Authors: Zihni, Ceniz, Mitsopoulos, Costas, Tavares, Ignatius A., Ridley, Anne J., Morris, Jonathan D.H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-03-2006; American Society for Biochemistry and Molecular Biology
• Subjects: Actin Depolymerizing Factors - chemistry; Actins - metabolism; Apoptosis; Binding Sites; Blotting, Northern; Caspase 2; Caspase 3; Caspases - metabolism; Catalysis; Cell Membrane - metabolism; Cytoskeleton - metabolism; DNA Fragmentation; Genes, Dominant; Humans; Immunoblotting; Immunoprecipitation; Intracellular Signaling Peptides and Proteins; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Kinase 4 - metabolism; Microscopy, Confocal; Microscopy, Fluorescence; Microtubules - metabolism; Models, Genetic; Plasmids - metabolism; Protein Kinases - metabolism; Protein Kinases - physiology; Protein Serine-Threonine Kinases - chemistry; Protein Serine-Threonine Kinases - metabolism; rho-Associated Kinases; Sorbitol - pharmacology; Staurosporine - chemistry; Staurosporine - pharmacology; Time Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M513769200

We have reported previously that human prostate-derived sterile 20-like kinase (PSK) 1 alters actin cytoskeletal organization and binds to microtubules, regulating their organization and stability. We have shown a structurally related protein kinase PSK2, which lacks a microtubule-binding site, activated c-Jun N-terminal kinase (JNK), and induced apoptotic morphological changes that include cell contraction, membrane blebbing, and apoptotic body formation. Apoptotic stimuli increased the catalytic activity of endogenous PSK2 and JNK, and dominant negative JNK or a physiological inhibitor of JNK blocked these apoptotic morphological responses to PSK2, demonstrating a requirement for JNK. PSK2 also stimulated the cleavage of Rho kinase-1 (ROCK-I), and the activity of ROCK-I was required for PSK2 to induce cell contraction and membrane blebbing. The activation of caspases was also needed for the induction of membrane blebbing by PSK2, which was itself a substrate for caspase 3. PSK2 therefore regulates apoptotic morphology associated with the execution phase of apoptosis, which involves dynamic reorganization of the actin cytoskeleton, via downstream targets that include JNK and ROCK-I. Our findings suggest that PSKs form a subgroup of sterile 20 (STE20)-like kinases that regulate different cytoskeletal processes.