Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-10-14
pubmed:abstractText
The mechanisms underlying downregulation of the cadherin/catenin complexes and beta-catenin signaling during tumor progression are not fully understood. We have analyzed the effect of oncogenic H-Ras on E-cadherin/catenin complex formation/stabilization and beta-catenin distribution in epidermal keratinocytes. Microinjection or stable expression of V12Ras into keratinocytes promotes the loss of E-cadherin and alpha-catenin and relocalization of beta-catenin to the cytoplasm and nucleus. Moreover, these effects are dependent on PI3K (phosphoinositide 3-OH kinase) activity. Interestingly, a strong association of p85alpha and p110alpha subunits of PI3K with beta-catenin is induced in V12Ras-expressing keratinocytes, and in vitro binding assays show a direct interaction between beta-catenin and p85alpha. Overexpression of either V12Ras or constitutively active p110alpha induces metabolic stabilization of beta-catenin and promotes its accumulation in cytoplasmic and nuclear pools. In addition, the interaction of beta-catenin with the adenomatous polyposis coli protein is blocked in V12Ras and p110alpha transformants though no changes in glycogen synthase kinase 3 beta activity could be detected. Nevertheless, in V12Ras transformants the in vivo phosphorylation of beta-catenin in Ser residues is strongly decreased. These results indicate that H-Ras activation induces the relocalization and cytoplasmic stabilization of beta-catenin by a mechanism involving its interaction with PI3K.
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenomatous Polyposis Coli Protein, http://linkedlifedata.com/resource/pubmed/chemical/Cadherins, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/Catna1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein p21(ras), http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/alpha Catenin, http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
pubmed:status
MEDLINE
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