期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 277, 期 27, 页码 24594-24600出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M201984200
关键词
-
资金
- NCI NIH HHS [CA91159] Funding Source: Medline
- NIAMS NIH HHS [AR44713] Funding Source: Medline
- NIGMS NIH HHS [GM55717] Funding Source: Medline
Cadherins function to promote adhesion between adjacent cells and play critical roles in such cellular processes as development, tissue maintenance, and tumor suppression. We previously demonstrated that heterotrimeric G proteins of the G(12) subfamily comprised of Galpha(12) and Galpha(13) interact with the cytoplasmic domain of cadherins and cause the release of the transcriptional activator beta-catenin (Meigs, T. E., Fields, T. A., McKee, D. D., and Casey, P. J. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 519-524). Because of the importance of beta-catenin in cadherin-mediated cell-cell adhesion, we examined whether G(12) subfamily proteins could also regulate cadherin function. The introduction of mutationally activated G(12) proteins into K562 cells expressing E-cadherin blocked cadherin-mediated cell adhesion in steady-state assays. Also, in breast cancer cells, the introduction of activated G(12) proteins blocked E-cadherin function in a fast aggregation assay. Aggregation mediated by a mutant cadherin that lacks G(12) binding ability was not affected by activated G(12) proteins, indicating a requirement for direct G(12)-cadherin interaction. Furthermore, in wound-filling assays in which ectopic expression of E-cadherin inhibits cell migration, the expression of activated G(12) proteins reversed the inhibition via a mechanism that was independent of G(12)-mediated Rho activation. These results validate the G(12)-cadherin interaction as a potentially important event in cell biology and suggest novel roles for G(12) proteins in the regulation of cadherin-mediated developmental events and in the loss of cadherin function that is characteristic of metastatic tumor progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据