Induction of apoptosis by the Ste20-like kinase SLK, a germinal center kinase that activates apoptosis signal-regulating kinase and p38.

@article{Hao2006, abstract = {Expression and activity of the germinal center kinase, Ste20-like kinase (SLK), are increased during kidney development and recovery from ischemic acute renal failure. In this study, we characterize the activation and functional role of SLK. SLK underwent dimerization via the C-terminal domain, and dimerization enhanced SLK activity. In contrast, the C-terminal domain of SLK did not dimerize with a related kinase, Mst1, and did not affect Mst1 activity. Phosphorylation/dephosphorylation of SLK were not associated with changes in kinase activity. SLK induced phosphorylation of apoptosis signal-regulating kinase-1 (ASK1) and increased ASK1 activity, indicating that ASK1 is a substrate of SLK. Moreover, SLK stimulated phosphorylation of p38 mitogen-activated protein kinase via ASK1, but not c-Jun N-terminal kinase nor extracellular signal-regulated kinase. Chemical anoxia and recovery during re-exposure to glucose (ischemia-reperfusion injury in cell culture) stimulated SLK activity. Overexpression of SLK enhanced anoxia/recovery-induced apoptosis, release of cytochrome c, and activities of caspase-8 and -9, and apoptosis was reduced significantly with p38 and caspase-9 inhibitors. Induction of the endoplasmic reticulum stress response by anoxia/recovery or tunicamycin (monitored by induction of Bip or Grp94 expression, phosphorylation of eukaryotic translation initiation factor 2alpha subunit, expression of CHOP, and activation of caspase-12) was attenuated in cells that overexpress SLK. Thus, SLK is an anoxia/recovery-dependent kinase that is activated via homodimerization and that signals via ASK1 and p38 to promote apoptosis. Attenuation of the protective aspects of the endoplasmic reticulum stress response by SLK may contribute to its proapoptotic effect.}, author = {Hao, Wen and Takano, Tomoko and Guillemette, Julie and Papillon, Joan and Ren, Guohui and Cybulsky, Andrey V. }, citeulike-article-id = {2054427}, doi = {10.1074/jbc.M511744200}, journal = {J Biol Chem}, keywords = {activation, aethiops, animal, apoptosis, article-predikin, calcium, caspase, catalytic, cell, cercopithecus, complementary, cos, cycle, cytochrome, densitometry, dimerization, dna, dog, domain, endoplasmic, enzyme, eukaryotic, factor-2, factors, glucose, growth, heat-shock, hepatocyte, hsp70, immunoblotting, immunoprecipitation, initiation, injury, ionophores, jnk, kinase, line, map, membrane, mitogen-activated, nerve, p38, phosphorylation, protein, protein-serine-threonine, proto-oncogene, rat, reperfusion, reticulum, structure, tertiary, tissue, tunicamycin}, month = {Feb}, number = {6}, pages = {3075--3084}, posted-at = {2007-12-04 03:22:12}, priority = {2}, title = {Induction of apoptosis by the Ste20-like kinase SLK, a germinal center kinase that activates apoptosis signal-regulating kinase and p38.}, url = {http://dx.doi.org/10.1074/jbc.M511744200}, volume = {281}, year = {2006} }

TY - JOUR ID - Hao2006 L3 - citeulike-article-id:2054427 TI - Induction of apoptosis by the Ste20-like kinase SLK, a germinal center kinase that activates apoptosis signal-regulating kinase and p38. JF - J Biol Chem VL - 281 IS - 6 SP - 3075 EP - 3084 N2 - Expression and activity of the germinal center kinase, Ste20-like kinase (SLK), are increased during kidney development and recovery from ischemic acute renal failure. In this study, we characterize the activation and functional role of SLK. SLK underwent dimerization via the C-terminal domain, and dimerization enhanced SLK activity. In contrast, the C-terminal domain of SLK did not dimerize with a related kinase, Mst1, and did not affect Mst1 activity. Phosphorylation/dephosphorylation of SLK were not associated with changes in kinase activity. SLK induced phosphorylation of apoptosis signal-regulating kinase-1 (ASK1) and increased ASK1 activity, indicating that ASK1 is a substrate of SLK. Moreover, SLK stimulated phosphorylation of p38 mitogen-activated protein kinase via ASK1, but not c-Jun N-terminal kinase nor extracellular signal-regulated kinase. Chemical anoxia and recovery during re-exposure to glucose (ischemia-reperfusion injury in cell culture) stimulated SLK activity. Overexpression of SLK enhanced anoxia/recovery-induced apoptosis, release of cytochrome c, and activities of caspase-8 and -9, and apoptosis was reduced significantly with p38 and caspase-9 inhibitors. Induction of the endoplasmic reticulum stress response by anoxia/recovery or tunicamycin (monitored by induction of Bip or Grp94 expression, phosphorylation of eukaryotic translation initiation factor 2alpha subunit, expression of CHOP, and activation of caspase-12) was attenuated in cells that overexpress SLK. Thus, SLK is an anoxia/recovery-dependent kinase that is activated via homodimerization and that signals via ASK1 and p38 to promote apoptosis. Attenuation of the protective aspects of the endoplasmic reticulum stress response by SLK may contribute to its proapoptotic effect. KW - activation KW - aethiops KW - animal KW - apoptosis KW - article-predikin KW - calcium KW - caspase KW - catalytic KW - cell KW - cercopithecus KW - complementary KW - cos KW - cycle KW - cytochrome KW - densitometry KW - dimerization KW - dna KW - dog KW - domain KW - endoplasmic KW - enzyme KW - eukaryotic KW - factor-2 KW - factors KW - glucose KW - growth KW - heat-shock KW - hepatocyte KW - hsp70 KW - immunoblotting KW - immunoprecipitation KW - initiation KW - injury KW - ionophores KW - jnk KW - kinase KW - line KW - map KW - membrane KW - mitogen-activated KW - nerve KW - p38 KW - phosphorylation KW - protein KW - protein-serine-threonine KW - proto-oncogene KW - rat KW - reperfusion KW - reticulum KW - structure KW - tertiary KW - tissue KW - tunicamycin AU - Hao, Wen AU - Takano, Tomoko AU - Guillemette, Julie AU - Papillon, Joan AU - Ren, Guohui AU - Cybulsky, Andrey PY - 2006/Feb// UR - http://dx.doi.org/10.1074/jbc.M511744200 ER -