2024-03-29T05:04:39Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/201062021-12-27T16:17:02Zcom_10261_25com_10261_1col_10261_278
DIGITAL.CSIC
author
Tin Chua, Boon
author
Gallego Ortega, David
author
Ramírez de Molina, Ana
author
Ullrich, Axel
author
Lacal, Juan Carlos
author
Downward, Julian
2010-01-15T13:16:55Z
2010-01-15T13:16:55Z
2009-12
Molecular Cancer 8(131): (2009)
1476-4598
http://hdl.handle.net/10261/20106
10.1186/1476-4598-8-131
20042122
Background: The serine/threonine kinase PKB/Akt plays essential role in various cellular processes including cell growth and proliferation, metabolism and cell survival. The importance of the Akt pathway is highlighted by the mutation of various components of the pathway such as the PTEN and PI3-kinase (P110α) in human cancers. In this paper, we employed an RNA interference library targeting all human kinases to screen for kinases involved in the regulation of Akt activation, in particular serine 473 phosphorylation. Here, we transfected the MDA-MB 468 breast cell line with the human kinome siRNA library and measured Akt activation using an antibody specific for phosphoserine 473 of Akt.
Results: The screen revealed that phosphorylation of Akt(ser473) can be regulated by more than 90 kinases. Interestingly, phosphorylation of Akt(ser473), but not thr308, can be severely reduced by inhibition of Choline kinase activity via siRNA or small molecule inhibitors. We show here that the regulation of Akt phosphorylation by Choline kinase is PI3K-independent. In addition, xenograft tumors treated with Choline kinase inhibitors demonstrated a statistically significant decrease in Akt(ser473) phosphorylation. Importantly, the reduction in phosphorylation correlates with regression of these xenograft tumors mouse model. Conclusion: High Choline kinase expression and activity has previously been implicated in tumor development and metastasis. The mechanism by which Choline kinase is involved in tumor formation is still not fully resolved. From our data, we proposed that Choline kinase plays a key role in regulating Akt(ser473) phosphorylation, thereby promoting cell survival and proliferation.
eng
openAccess
Regulation of Akt (ser473) phosphorylation by Choline kinase in breast carcinoma cells
artículo
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
URL
https://digital.csic.es/bitstream/10261/20106/1/1476-4598-8-131.pdf
File
MD5
bc3fd865127568b3025a59152192bec2
979793
application/pdf
1476-4598-8-131.pdf
URL
https://digital.csic.es/bitstream/10261/20106/4/1476-4598-8-131.pdf.txt
File
MD5
d5aec2f80fed8c96d366e8816d7b8d9a
44486
text/plain
1476-4598-8-131.pdf.txt