Linked Life Data

12478298

Source:http://linkedlifedata.com/resource/pubmed/id/12478298

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6916
pubmed:dateCreated
2002-12-12
pubmed:abstractText
Evolution of human organismal complexity from a relatively small number of genes--only approximately twice that of worm or fly--is explained mainly by mechanisms generating multiple proteins from a single gene, the most prevalent of which is alternative pre-messenger-RNA splicing. Appropriate spatial and temporal generation of splice variants demands that alternative splicing be subject to extensive regulation, similar to transcriptional control. Activation by extracellular cues of several cellular signalling pathways can indeed regulate alternative splicing. Here we address the link between signal transduction and splice regulation. We show that the nuclear RNA-binding protein Sam68 is a new extracellular signal-regulated kinase (ERK) target. It binds exonic splice-regulatory elements of an alternatively spliced exon that is physiologically regulated by the Ras signalling pathway, namely exon v5 of CD44. Forced expression of Sam68 enhanced ERK-mediated inclusion of the v5-exon sequence in mRNA. This enhancement was impaired by mutation of ERK-phosphorylation sites in Sam68, whereas ERK phosphorylation of Sam68 stimulated splicing of the v5 exon in vitro. Finally, Ras-pathway-induced alternative splicing of the endogenous CD44-v5 exon was abolished by suppression of Sam68 expression. Our data define Sam68 as a prototype regulator of alternative splicing whose function depends on protein modification in response to extracellular cues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
420
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
691-5
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Signal-dependent regulation of splicing via phosphorylation of Sam68.
pubmed:affiliation
Forschungszentrum Karlsruhe GmbH, Institut für Toxikologie und Genetik, Postfach 3640, D-76021 Karlsruhe, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't