| BacMam-enabled LanthaScreen cellular assays for PI3K/Akt pathway compound profiling in disease-relevant cell backgrounds. | |
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MedLine Citation:
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PMID: 20145103 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The authors recently reported the development and application of multiple LanthaScreen cellular assays to interrogate specific steps within the PI3K/Akt pathway. The importance of this signaling cascade in regulating fundamental aspects of cell growth and survival, as well as in the progression of cancer, underscores the need for portable cell-based assays for compound profiling in multiple disease-relevant cell backgrounds. To meet this need, the authors have now expanded their LanthaScreen assay platform across a variety of cell types using a gene delivery technology known as BacMam. Here, they have demonstrated the successful detection of Akt-dependent phosphorylation of PRAS40 at Thr246 in 10 different cell lines harboring mutations known to activate the PI3K/Akt pathway. In addition, they generated inhibitory profiles of 17 known pathway inhibitors in these same cells to validate the approach of using the BacMam-enabled LanthaScreen cellular assay format to rapidly profile compounds in disease-relevant cell types. Importantly, their results provide a broad illustration of how the genetic alterations that affect PI3K/Akt signaling can also influence the inhibitory profile of a given compound. |
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Authors:
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Coby B Carlson; Michael J Mashock; Kun Bi |
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Publication Detail:
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Type: Journal Article Date: 2010-02-09 |
Journal Detail:
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Title: Journal of biomolecular screening Volume: 15 ISSN: 1552-454X ISO Abbreviation: J Biomol Screen Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-09 Completed Date: 2010-06-28 Revised Date: 2011-05-23 |
Medline Journal Info:
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Nlm Unique ID: 9612112 Medline TA: J Biomol Screen Country: United States |
Other Details:
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Languages: eng Pagination: 327-34 Citation Subset: IM |
Affiliation:
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Invitrogen Discovery Assays and Services, Cell Systems Division, Invitrogen (Part of Life Technologies), Madison, Wisconsin 53719, USA. coby.carlson@invitrogen.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biological Assay
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methods* Cell Line, Tumor Green Fluorescent Proteins / metabolism Humans Inhibitory Concentration 50 Mutation / genetics Neoplasms / enzymology*, pathology Phosphatidylinositol 3-Kinases / antagonists & inhibitors, metabolism* Protein Kinase Inhibitors / analysis*, pharmacology* Proto-Oncogene Proteins c-akt / antagonists & inhibitors, metabolism* Recombinant Fusion Proteins / metabolism Signal Transduction / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Protein Kinase Inhibitors; 0/Recombinant Fusion Proteins; 147336-22-9/Green Fluorescent Proteins; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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