Linked Life Data

15674841

Source:http://linkedlifedata.com/resource/pubmed/id/15674841

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-2-1
pubmed:abstractText
While the process of the Ah receptor activation leading to cytochrome P450 induction has been well studied, the mechanism and the process through which the Ah receptor activates tyrosine kinases, within a few minutes of its ligand binding, is not known. Previously, it was reported by Tannheimer et al. (Carcinogenesis 1998; 19:1291-1297) that TCDD causes rapid induction of tyrosine phosphorylation activities in the MCF10A human mammary epithelial cell line. To study the mechanistic aspect of this phenomenon, particularly that occurs within a few minutes after administration, we first studied the effect of insulin on MCF10A under serum free conditions with added EGF. The addition of insulin induced a rapid (5 min) tyrosine phosphorylation on several 160-190 kDa proteins which was followed by significant dephosphorylation activities on these proteins by 15 min. TCDD increased the rate of tyrosine phosphorylation on those proteins but at 15 min, the level of phosphorylation was still high. When insulin and TCDD were added together, the ability of insulin to induce de-phosphorylation by 15 min disappeared. Such an action of TCDD was accompanied by an increase in the titer of the activated form of Src kinase (i.e. c-Src protein with 418 tyrosine phosphorylation), and a concomitant decrease in the level of 529 tyrosine phosphorylated form (an inactivated form). The TCDD-induced activation of c-Src could be blocked by pretreated MCF10A cells with antisense oligonucleotides against c-src or with a specific inhibitor of Src kinase, PP-2. These results support the conclusion that c-Src kinase is at least one of the earliest and the most upstream components of toxic signaling of the Ah-receptor activated by TCDD through the post-transcriptional process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1095-6670
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
313-21
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Studies on the mechanism of rapid activation of protein tyrosine phosphorylation activities, particularly c-Src kinase, by TCDD in MCF10A.
pubmed:affiliation
Department of Environmental Toxicology and the Center for Environmental Health Sciences, University of California, One Shields Ave, Davis, CA 95616, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.