Leucine-rich repeat-containing G-protein coupled receptor 5/GPR49 activates G12/13-Rho GTPase pathway = LGR5에 의한 G12/13-Rho 신호전달계의 활성화

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Title
Leucine-rich repeat-containing G-protein coupled receptor 5/GPR49 activates G12/13-Rho GTPase pathway = LGR5에 의한 G12/13-Rho 신호전달계의 활성화
Author(s)
Mi-So Kwon; Bioh Park; H M Kim; Sunhong Kim
Bibliographic Citation
Molecules and Cells, vol. 36, no. 3, pp. 267-272
Publication Year
2013
Abstract
Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5/GPR49) is highly expressed in adult stem cells of various tissues, such as intestine, hair follicles, and stomach. LGR5 is also overexpressed in some colon and ovarian tumors. Recent reports show that R-spondin (RSPO) family ligands bind to and activate LGR5, enhancing canonical Wnt signaling via the interaction with LRP5/6 and Frizzled. The identity of heterotrimeric G-proteins coupled to LGR5, however, remains unclear. Here, we show that Rho GTPase is a downstream target of LGR5. Overexpression of LGR5 induced SRF-RE luciferase activity, a reporter of Rho signaling. RSPOs, ligands for LGR4, LGR5, and LGR6, however, did not induce SRF-RE reporter activity in the presence of LGR5. Consistently, LGR5-induced activity of the SRF-RE reporter was inhibited by Rho inhibitor C3 transferase and RhoA N19 mutant, and knockdown of Gα12/13 genes blocked the reporter activity induced by LGR5. In addition, focal adhesion kinase, NF-κB and c-fos, targets of Rho GTPase, were shown to be regulated by LGR5. Here, we have demonstrated, for the first time, that LGR5 is coupled to the Rho pathway through G12/13 signaling.
Keyword
FAKLGR5NFkappaBRho
ISSN
1016-8478
Publisher
South Korea
DOI
http://dx.doi.org/10.1007/s10059-013-0173-z
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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