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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1997-4-22
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pubmed:abstractText |
DAP-kinase was initially identified as a gene whose anti-sense-mediated reduced expression protected HeLa cells from interferon-gamma-induced programmed cell death. It was cloned in our laboratory by a functional gene selection approach. According to its amino acid sequence, this 160 kDa protein was predicted to be a novel type of calmodulin-regulated serine/threonine kinase which carries ankyrin repeats and the death domain. In this work we have shown that the kinase was autophosphorylated and capable of phosphorylating an exogenous substrate in a Ca2+/calmodulin-dependent manner. We proved that calmodulin binds directly to the recombinant kinase, and generated a constitutively active kinase mutant by the deletion of the calmodulin-regulatory domain. By immunostaining and biochemical fractionations we demonstrated that the kinase is localized to the cytoskeleton, in association with the microfilament system, and mapped a region within the protein which is responsible for binding to the cytoskeleton. Several assays attributed a cell death function to the gene. Ectopic expression of wild-type DAP-kinase induced the death of target cells, and the killing property depended strictly on the status of the intrinsic kinase activity. Conversely, a catalytically inactive mutant that carried a lysine to alanine substitution within the kinase domain, displayed dominant-negative features and protected cells from interferon-gamma-induced cell death. DAP-kinase is therefore a novel cytoskeletal-associated cell death serine/threonine kinase whose activation by Ca2+/calmodulin may be linked to the biochemical mechanism underlying the cytoskeletal alterations that occur during cell death.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-1309441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-1319065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-1713127,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-1901424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-1917967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-1956325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-2202734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-2787530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-3171180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7482697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7499268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7531702,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7536190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7538907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7538908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7542648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7542668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7638903,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7657168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7720065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7758105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7828849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7940758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7958843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-7961935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8087842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8242741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8263039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8283033,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8366104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8383624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8560270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8670891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9118961-8791485
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
998-1008
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:9118961-Actin Cytoskeleton,
pubmed-meshheading:9118961-Apoptosis,
pubmed-meshheading:9118961-Apoptosis Regulatory Proteins,
pubmed-meshheading:9118961-Calcium,
pubmed-meshheading:9118961-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9118961-Calmodulin,
pubmed-meshheading:9118961-Catalysis,
pubmed-meshheading:9118961-Cytoskeleton,
pubmed-meshheading:9118961-Fluorescent Antibody Technique,
pubmed-meshheading:9118961-Gene Expression,
pubmed-meshheading:9118961-HeLa Cells,
pubmed-meshheading:9118961-Humans,
pubmed-meshheading:9118961-Immunoblotting,
pubmed-meshheading:9118961-Immunohistochemistry,
pubmed-meshheading:9118961-Interferon-gamma,
pubmed-meshheading:9118961-Mutagenesis, Site-Directed,
pubmed-meshheading:9118961-Mutation,
pubmed-meshheading:9118961-Phosphorylation,
pubmed-meshheading:9118961-Protein Binding,
pubmed-meshheading:9118961-Recombinant Proteins
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pubmed:year |
1997
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pubmed:articleTitle |
DAP-kinase is a Ca2+/calmodulin-dependent, cytoskeletal-associated protein kinase, with cell death-inducing functions that depend on its catalytic activity.
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pubmed:affiliation |
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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