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Article: Akt blocks the tumor suppressor activity of LKB1 by promoting phosphorylation-dependent nuclear retention through 14-3-3 proteins
Title | Akt blocks the tumor suppressor activity of LKB1 by promoting phosphorylation-dependent nuclear retention through 14-3-3 proteins |
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Authors | |
Keywords | Protein 14-3-3 Protein kinase B Animal experiment Breast cancer Breast carcinogenesis |
Issue Date | 2012 |
Publisher | E-Century Publishing Corporation. The Journal's web site is located at http://www.ajtr.org |
Citation | American Journal of Translational Research, 2012, v. 4 n. 2, p. 175-186 How to Cite? |
Abstract | The survival kinase Akt and the tumor suppressor LKB1 elicit opposite effects on cell proliferation and tumorigenesis. The present study demonstrates that Akt acts as an upstream kinase of LKB1 to promote the phosphorylation at Ser334 and facilitate its binding to 14-3-3 proteins, resulting in a decreased interaction with STE20-related adaptor protein alpha (STRADalpha) and an enhanced nuclear accumulation of LKB1. The S334A mutant of LKB1 exhibits impaired binding with 14-3-3 proteins and is localized predominantly in the cytoplasm, whereas the phosphorylation-mimic mutant, S334D, is sequestrated in the nuclei and unable to elicit the tumor suppressor function. On the other hand, S334A exerts more potent activity than wild type LKB1 in inhibiting the breast cancer cell proliferation and tumor growth in mice. These findings suggest that Akt blocks the anti-growth signal of LKB1 by triggering a phosphorylation-dependent nuclear sequestration of LKB1 through 14-3-3 proteins. |
Persistent Identifier | http://hdl.handle.net/10722/163480 |
ISSN | 2023 Impact Factor: 1.7 2020 SCImago Journal Rankings: 1.027 |
PubMed Central ID | |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Liu, L | en_HK |
dc.contributor.author | Siu, FM | en_HK |
dc.contributor.author | Che, CM | en_HK |
dc.contributor.author | Xu, A | en_HK |
dc.contributor.author | Wang, Y | en_HK |
dc.date.accessioned | 2012-09-05T05:31:50Z | - |
dc.date.available | 2012-09-05T05:31:50Z | - |
dc.date.issued | 2012 | en_HK |
dc.identifier.citation | American Journal of Translational Research, 2012, v. 4 n. 2, p. 175-186 | en_HK |
dc.identifier.issn | 1943-8141 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/163480 | - |
dc.description.abstract | The survival kinase Akt and the tumor suppressor LKB1 elicit opposite effects on cell proliferation and tumorigenesis. The present study demonstrates that Akt acts as an upstream kinase of LKB1 to promote the phosphorylation at Ser334 and facilitate its binding to 14-3-3 proteins, resulting in a decreased interaction with STE20-related adaptor protein alpha (STRADalpha) and an enhanced nuclear accumulation of LKB1. The S334A mutant of LKB1 exhibits impaired binding with 14-3-3 proteins and is localized predominantly in the cytoplasm, whereas the phosphorylation-mimic mutant, S334D, is sequestrated in the nuclei and unable to elicit the tumor suppressor function. On the other hand, S334A exerts more potent activity than wild type LKB1 in inhibiting the breast cancer cell proliferation and tumor growth in mice. These findings suggest that Akt blocks the anti-growth signal of LKB1 by triggering a phosphorylation-dependent nuclear sequestration of LKB1 through 14-3-3 proteins. | en_HK |
dc.language | eng | en_US |
dc.publisher | E-Century Publishing Corporation. The Journal's web site is located at http://www.ajtr.org | en_HK |
dc.relation.ispartof | American Journal of Translational Research | en_HK |
dc.subject | Protein 14-3-3 | en_HK |
dc.subject | Protein kinase B | en_HK |
dc.subject | Animal experiment | en_HK |
dc.subject | Breast cancer | en_HK |
dc.subject | Breast carcinogenesis | en_HK |
dc.title | Akt blocks the tumor suppressor activity of LKB1 by promoting phosphorylation-dependent nuclear retention through 14-3-3 proteins | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Siu, FM: fmsiu@hku.hk | en_HK |
dc.identifier.email | Che, CM: cmche@hku.hk | en_HK |
dc.identifier.email | Xu, A: amxu@hku.hk | - |
dc.identifier.email | Wang, Y: yuwanghk@hku.hk | - |
dc.identifier.authority | Siu, FM=rp00776 | en_HK |
dc.identifier.authority | Che, CM=rp00670 | en_HK |
dc.description.nature | published_or_final_version | en_US |
dc.identifier.pmid | 22611470 | - |
dc.identifier.pmcid | PMC3353533 | - |
dc.identifier.scopus | eid_2-s2.0-84860178975 | en_HK |
dc.identifier.hkuros | 204848 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-84860178975&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 4 | en_HK |
dc.identifier.issue | 2 | en_HK |
dc.identifier.spage | 175 | en_HK |
dc.identifier.epage | 186 | en_HK |
dc.identifier.isi | WOS:000318278200004 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Wang, Y=34973733700 | en_HK |
dc.identifier.scopusauthorid | Xu, A=7202655409 | en_HK |
dc.identifier.scopusauthorid | Che, CM=55195481700 | en_HK |
dc.identifier.scopusauthorid | Siu, FM=55195027400 | en_HK |
dc.identifier.scopusauthorid | Liu, L=21737444900 | en_HK |
dc.identifier.issnl | 1943-8141 | - |