LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity
<p>Abstract</p> <p>Background</p> <p>Germline mutations in <it>LKB1 </it>result in Peutz-Jeghers Syndrome characterized by intestinal hamartomas and increased incidence of epithelial cancers. <it>LKB1 </it>encodes a serine/threonine kinase that p...
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| Format: | Article |
| Language: | English |
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BMC
2010-10-01
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| Series: | BMC Cell Biology |
| Online Access: | http://www.biomedcentral.com/1471-2121/11/77 |
| _version_ | 1818857669253922816 |
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| author | Hall Alan Omelchenko Tatiana Xu Xiaojian |
| author_facet | Hall Alan Omelchenko Tatiana Xu Xiaojian |
| author_sort | Hall Alan |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Germline mutations in <it>LKB1 </it>result in Peutz-Jeghers Syndrome characterized by intestinal hamartomas and increased incidence of epithelial cancers. <it>LKB1 </it>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 <it>C. elegans</it>, while activation of LKB1 in mammalian epithelial cells induces the polarized assembly of actin filaments.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>This study reveals that LKB1 regulates the actin cytoskeleton through a Dbl/Rho pathway.</p> |
| first_indexed | 2024-12-19T08:44:04Z |
| format | Article |
| id | doaj.art-5afc36bc52a743039a7d3eeee941d93d |
| institution | Directory Open Access Journal |
| issn | 1471-2121 |
| language | English |
| last_indexed | 2024-12-19T08:44:04Z |
| publishDate | 2010-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cell Biology |
| spelling | doaj.art-5afc36bc52a743039a7d3eeee941d93d2022-12-21T20:28:52ZengBMCBMC Cell Biology1471-21212010-10-011117710.1186/1471-2121-11-77LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activityHall AlanOmelchenko TatianaXu Xiaojian<p>Abstract</p> <p>Background</p> <p>Germline mutations in <it>LKB1 </it>result in Peutz-Jeghers Syndrome characterized by intestinal hamartomas and increased incidence of epithelial cancers. <it>LKB1 </it>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 <it>C. elegans</it>, while activation of LKB1 in mammalian epithelial cells induces the polarized assembly of actin filaments.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>This study reveals that LKB1 regulates the actin cytoskeleton through a Dbl/Rho pathway.</p>http://www.biomedcentral.com/1471-2121/11/77 |
| spellingShingle | Hall Alan Omelchenko Tatiana Xu Xiaojian LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity BMC Cell Biology |
| title | LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity |
| title_full | LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity |
| title_fullStr | LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity |
| title_full_unstemmed | LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity |
| title_short | LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity |
| title_sort | lkb1 tumor suppressor protein regulates actin filament assembly through rho and its exchange factor dbl independently of kinase activity |
| url | http://www.biomedcentral.com/1471-2121/11/77 |
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