LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity Journal Article
| Authors: | Xu, X.; Omelchenko, T.; Hall, A. |
| Article Title: | LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity |
| Abstract: | Background: Germline 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.Results: To 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.Conclusions: This study reveals that LKB1 regulates the actin cytoskeleton through a Dbl/Rho pathway. © 2010 Xu et al; licensee BioMed Central Ltd. |
| Keywords: | signal transduction; controlled study; protein expression; dna binding protein; human cell; genetics; mutation; dna-binding proteins; metabolism; mammalia; actin; embryo; small interfering rna; rna, small interfering; transcription factor; protein interaction; enzyme activation; pathology; enzyme activity; hela cell; hela cells; protein serine threonine kinase; transcription factors; cell transformation, neoplastic; enzyme regulation; cell transformation; protein-serine-threonine kinases; enzyme inactivation; tumor suppressor proteins; carcinoma; transgene; caenorhabditis elegans; tumor suppressor protein; intestine tumor; intestinal neoplasms; cytoskeleton; rho guanine nucleotide binding protein; rho gtp-binding proteins; transgenes; cytoskeleton protein; ezrin; cytoskeletal proteins; microfilaments; vesicular transport adaptor protein; adaptor proteins, vesicular transport; guanine nucleotide exchange factor; adaptor protein; peutz-jeghers syndrome; peutz jeghers syndrome; protein kinase lkb1; stk11 protein, human; strad protein, human; vezf1 protein, human; actin filament; focal adhesion; stress fiber; microfilament |
| Journal Title: | BMC Cell Biology |
| Volume: | 11 |
| ISSN: | 1471-2121 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2010-10-12 |
| Start Page: | 77 |
| Language: | English |
| DOI: | 10.1186/1471-2121-11-77 |
| PUBMED: | 20939895 |
| PROVIDER: | scopus |
| PMCID: | PMC2964536 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "Art. No.: 77" - "CODEN: BCBMA" - "Source: Scopus" |
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