Linked Life Data

17158878

Source:http://linkedlifedata.com/resource/pubmed/id/17158878

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pubmed-article:17158878pubmed:abstractTextWe have demonstrated previously that full-length prostate-derived sterile 20-like kinase 1-alpha (PSK1-alpha) binds to microtubules via its C terminus and regulates their organization and stability independently of its catalytic activity. Here we have shown that apoptotic and microtubule-disrupting agents promote catalytic activation, C-terminal cleavage, and nuclear translocation of endogenous phosphoserine 181 PSK1-alpha and activated N-terminal PSK1-alpha-induced apoptosis. PSK1-alpha, unlike its novel isoform PSK1-beta, stimulated the c-Jun N-terminal kinase (JNK) pathway, and the nuclear localization of PSK1-alpha and its induction of cell contraction, membrane blebbing, and apoptotic body formation were dependent on JNK activity. PSK1-alpha was also a caspase substrate, and the broad spectrum caspase inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone or mutation of a putative caspase recognition motif ((916)DPGD(919)) blocked nuclear localization of PSK1-alpha and its induction of membrane blebs. Additional inhibition of caspase 9 was needed to prevent cell contraction. PSK1-alpha is therefore a bifunctional kinase that associates with microtubules, and JNK- and caspase-mediated removal of its C-terminal microtubule-binding domain permits nuclear translocation of the N-terminal region of PSK1-alpha and its induction of apoptosis.lld:pubmed
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pubmed-article:17158878pubmed:dateRevised2009-11-19lld:pubmed
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pubmed-article:17158878pubmed:articleTitleProstate-derived sterile 20-like kinase 1-alpha induces apoptosis. JNK- and caspase-dependent nuclear localization is a requirement for membrane blebbing.lld:pubmed
pubmed-article:17158878pubmed:affiliationKings College London, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, United Kingdom.lld:pubmed
pubmed-article:17158878pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:17158878pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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