Loading...
|
Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/2165
|
| Title: | Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation |
| Authors: | Tsai, YT;Su, YH;Fang, SS;Huang, TN;Qiu, Y;Jou, YS;Shih, HM;Kung, HJ;Chen, RH |
| Contributors: | Division of Molecular and Genomic Medicine |
| 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 effecters 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, WE, 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. |
| Keywords: | Biochemistry & Molecular Biology;Cell Biology |
| Date: | 2000-03 |
| Relation: | Molecular and Cellular Biology. 2000 Mar;20(6):2043-2054. |
| Link to: | http://dx.doi.org/10.1128/MCB.20.6.2043-2054.2000 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0270-7306&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000085545200014 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0034002476 |
| Appears in Collections: | [施修明] 期刊論文
[周玉山(1996-2005)] 期刊論文
[龔行健] 期刊論文
|
Files in This Item:
| File |
Description |
Size | Format | |
|---|
| 000085545200014.pdf | | 2552Kb | Adobe PDF | 1138 | View/Open |
|
All items in NHRI are protected by copyright, with all rights reserved.
|
