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• W2156449667 endingPage "2054" @default.
• W2156449667 startingPage "2043" @default.
• W2156449667 abstract "Etk (also called Bmx) is a member of the Btk tyrosine kinase family and is expressed in a variety of hematopoietic, epithelial, and endothelial cells. We have explored biological functions, regulators, and effectors of Etk. Coexpression of v-Src and Etk led to a transphosphorylation on tyrosine 566 of Etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of Etk. STAT3, which was previously shown to be activated by Etk, associated with Etk in vivo. To investigate whether Etk could mediate v-Src-induced activation of STAT3 and cell transformation, we overexpressed a dominant-negative mutant of Etk in an immortalized, untransformed rat liver epithelial cell line, WB, which contains endogenous Etk. Dominant-negative inactivation of Etk not only blocked v-Src-induced tyrosine phosphorylation and activation of STAT3 but also caused a great reduction in the transforming activity of v-Src. In NIH3T3 cells, although Etk did not itself induce transformation, it effectively enhanced the transforming ability of a partially active c-Src mutant (c-Src378G). Furthermore, Etk activated STAT3-mediated gene expression in synergy with this Src mutant. Our findings thus indicate that Etk is a critical mediator of Src-induced cell transformation and STAT3 activation. The role of STAT3 in Etk-mediated transformation was also examined. Expression of Etk in a human hepatoma cell line Hep3B resulted in a significant increase in its transforming ability, and this effect was abrogated by dominant-negative inhibition of STAT3. These data strongly suggest that Etk links Src to STAT3 activation. Furthermore, Src-Etk-STAT3 is an important pathway in cellular transformation." @default.
• W2156449667 created "2016-06-24" @default.
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• W2156449667 date "2000-03-01" @default.
• W2156449667 modified "2023-10-16" @default.
• W2156449667 title "Etk, a Btk Family Tyrosine Kinase, Mediates Cellular Transformation by Linking Src to STAT3 Activation" @default.
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• W2156449667 doi "https://doi.org/10.1128/mcb.20.6.2043-2054.2000" @default.
• W2156449667 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/110821" @default.
• W2156449667 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10688651" @default.
• W2156449667 hasPublicationYear "2000" @default.
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