LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity

BMC Cell Biology

Research Article

Alan Hall¹  Xiaojian Xu¹  Tatiana Omelchenko¹ 

[1] Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10065, New York, NY, USA;

关键词: Actin Filament;    Stress Fiber;    Guanine Nucleotide Exchange Factor;    Stress Fiber Formation;    Actin Filament Bundle;   

DOI  :  10.1186/1471-2121-11-77

 received in 2010-03-02, accepted in 2010-10-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGermline mutations in LKB1 result in Peutz-Jeghers Syndrome characterized by intestinal hamartomas and increased incidence of epithelial cancers. LKB1 encodes a serine/threonine kinase that plays an important role in regulating energy metabolism through the AMPK/mTOR signaling pathway. In addition, LKB1 is homologous to PAR-4, a polarity protein first described in C. elegans, while activation of LKB1 in mammalian epithelial cells induces the polarized assembly of actin filaments.ResultsTo explore the mechanism by which LKB1 interacts with the actin cytoskeleton, we introduced LKB1 into HeLa cells that lack endogenous LKB1. This results in activation of the small GTPase Rho and the assembly of linear actin filaments associated with focal adhesions. These effects on the actin cytoskeleton are attenuated by siRNA-mediated depletion of the guanine nucleotide exchange factor Dbl. Co-expression of the LKB1 with the adaptor protein STRAD induces actin filament puncta associated with phospho-ezrin.ConclusionsThis study reveals that LKB1 regulates the actin cytoskeleton through a Dbl/Rho pathway.

【 授权许可】

Unknown   
© Xu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.