Linked Life Data

14722104

Source:http://linkedlifedata.com/resource/pubmed/id/14722104

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2004-3-22
pubmed:abstractText
The Wnt/beta-catenin signaling pathway is important in both development and cancer. Casein kinase Iepsilon (CKIepsilon) is a positive regulator of the canonical Wnt pathway. CKIepsilon itself can be regulated in vitro by inhibitory autophosphorylation, and recent data suggest that in vivo kinase activity can be regulated by extracellular stimuli. We show here that the phosphorylation state and kinase activity of CKIepsilon are directly regulated by Wnt signaling. Coexpression of XWnt-8 or addition of soluble Wnt-3a ligand led to a significant and rapid increase in the activity of endogenous CKIepsilon. The increase in CKIepsilon activity is the result of decreased inhibitory autophosphorylation because it is abolished by preincubation of immunoprecipitated kinase with ATP. Furthermore, mutation of CKIepsilon inhibitory autophosphorylation sites creates a kinase termed CKIepsilon(MM2) that is significantly more active than CKIepsilon and is not activated further upon Wnt stimulation. Autoinhibition of CKIepsilon is biologically relevant because CKIepsilon(MM2) is more effective than CKIepsilon at activating transcription from a Lef1-dependent promoter. Finally, CKIepsilon(MM2) expression in Xenopus embryos induces both axis duplication and additional developmental abnormalities. The data suggest that Wnt signaling activates CKIepsilon by causing transient dephosphorylation of critical inhibitory sites present in the carboxyl-terminal domain of the kinase. Activation of the Wnt pathway may therefore stimulate a cellular phosphatase to dephosphorylate and activate CKIepsilon
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13011-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14722104-Adenosine Triphosphate, pubmed-meshheading:14722104-Animals, pubmed-meshheading:14722104-Casein Kinases, pubmed-meshheading:14722104-Cell Line, pubmed-meshheading:14722104-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:14722104-Gene Expression Regulation, Enzymologic, pubmed-meshheading:14722104-Genes, Reporter, pubmed-meshheading:14722104-Humans, pubmed-meshheading:14722104-Ligands, pubmed-meshheading:14722104-Luciferases, pubmed-meshheading:14722104-Mice, pubmed-meshheading:14722104-Mutation, pubmed-meshheading:14722104-Phosphorylation, pubmed-meshheading:14722104-Plasmids, pubmed-meshheading:14722104-Precipitin Tests, pubmed-meshheading:14722104-Protein Kinases, pubmed-meshheading:14722104-Proto-Oncogene Proteins, pubmed-meshheading:14722104-Signal Transduction, pubmed-meshheading:14722104-Time Factors, pubmed-meshheading:14722104-Transfection, pubmed-meshheading:14722104-Wnt Proteins, pubmed-meshheading:14722104-Xenopus, pubmed-meshheading:14722104-Xenopus Proteins, pubmed-meshheading:14722104-Zebrafish Proteins
pubmed:year
2004
pubmed:articleTitle
Regulation of casein kinase I epsilon activity by Wnt signaling.
pubmed:affiliation
Department of Oncological Sciences and the Center for Children, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't