Linked Life Data

15133026

Source:http://linkedlifedata.com/resource/pubmed/id/15133026

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2004-7-5
pubmed:abstractText
The transforming growth factor-beta (TGF-beta) signaling pathway is known to be involved in a wide range of biological events, including development, cellular differentiation, apoptosis, and oncogenesis. The TGF-beta signal is mediated by ligand binding to the type II receptor, leading to the recruitment and activation of the type I receptor, and subsequent activation of a family of intracellular signal transducing proteins called Smads. Here we report a regulatory role for casein kinase Iepsilon (CKIepsilon) in the TGF-beta signaling cascade. We find that CKIepsilon binds to all Smads and the cytoplasmic domains of the type I and type II receptors both in vitro and in vivo. The interaction of CKIepsilon with the type I and type II receptors is independent of TGF-beta stimulation, whereas the CKIepsilon/Smad interaction is transiently disrupted by ligand treatment. Additionally, CKIepsilon is able to phosphorylate the receptor-activated Smads (Smads 1-3 and 5) and the type II receptor in vitro. Transcriptional reporter assays reveal that transient overexpression of wild type CKIepsilon dramatically reduces basal reporter activity but enhances TGF-beta-stimulated transcription. Furthermore, overexpression of a kinase-dead mutant of CKIepsilon inhibits both basal and ligand-induced transcription, whereas inhibition of endogenous CKI catalytic activity with IC261 blocks only TGF-beta-stimulated reporter activity. Finally, knocking down CKIepsilon protein levels results in a significant increase in basal and TGF-beta-induced transcription. These results suggest that CKIepsilon plays a ligand-dependent, differential, and dual regulatory role within the TGF-beta signaling pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29236-46
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15133026-Animals, pubmed-meshheading:15133026-Casein Kinases, pubmed-meshheading:15133026-Cell Line, pubmed-meshheading:15133026-DNA-Binding Proteins, pubmed-meshheading:15133026-Genes, Reporter, pubmed-meshheading:15133026-Humans, pubmed-meshheading:15133026-Ligands, pubmed-meshheading:15133026-Protein Binding, pubmed-meshheading:15133026-Protein Isoforms, pubmed-meshheading:15133026-Protein Kinases, pubmed-meshheading:15133026-RNA, Small Interfering, pubmed-meshheading:15133026-Receptors, Transforming Growth Factor beta, pubmed-meshheading:15133026-Recombinant Fusion Proteins, pubmed-meshheading:15133026-Signal Transduction, pubmed-meshheading:15133026-Smad Proteins, pubmed-meshheading:15133026-Trans-Activators, pubmed-meshheading:15133026-Transcription, Genetic, pubmed-meshheading:15133026-Transforming Growth Factor beta
pubmed:year
2004
pubmed:articleTitle
Casein kinase Iepsilon plays a functional role in the transforming growth factor-beta signaling pathway.
pubmed:affiliation
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.