A new chemical probe for phosphatidylinositol kinase activity

From National Research Council Canada

DOI	Resolve DOI: https://doi.org/10.1002/cbic.201402155
Author	Search for: Sherratt, Allison R.¹; Search for: Nasheri ardakan, Neda¹; Search for: McKay, Craig S.¹; Search for: O'Hara, Shifawn¹; Search for: Hunt, Ashly¹; Search for: Ning, Zhibin; Search for: Figeys, Daniel; Search for: Goto, Nathalie K.; Search for: Pezacki, John Paul¹
Affiliation	National Research Council of Canada. Medical Devices
Format	Text, Article
Subject	phosphatidylinositol 3 kinase; phosphatidylinositol 3 kinase 110alpha; phosphatidylinositol kinase; phosphatidylinositol kinase 2alpha; phosphatidylinositol kinase 3alpha; phosphatidylinositol kinase 3beta; unclassified drug; wortmannin; breast cancer cell line; cancer cell line; chemical labeling; competitive inhibition; enzyme activity; enzyme inhibition; female; genotype; hepatitis C; Hepatitis C virus; human cell; liver cell carcinoma; liver disease; liver transplantation; molecular probe; photoactivation; photoreactivation; PIK BPyne; primed in situ labeling; protein analysis; protein function; uterine cervix cancer; virus replication; Western blotting; Hepatitis C virus
Abstract	Phosphatidylinositol kinases (PIKs) are key enzymatic regulators of membrane phospholipids and membrane environments that control many aspects of cellular function, from signal transduction to secretion, through the Golgi apparatus. Here, we have developed a photoreactive "clickable" probe, PIK-BPyne, to report the activity of PIKs. We investigated the selectivity and efficiency of the probe to both inhibit and label PIKs, and we compared PIK-BPyne to a wortmannin activity-based probe also known to target PIKs. We found that PIK-BPyne can act as an effective in situ activity-based probe, and for the first time, report changes in PI4K-IIIβ activity induced by the hepatitis C virus. These results establish the utility of PIK-BPyne for activity-based protein profiling studies of PIK function in native biological systems. Active PIKs: Phosphatidylinositol kinases (PIKs) are key enzymatic regulators of membrane phospholipids and environments that control many aspects of cellular function, from signal transduction to secretion. We developed a photoreactive "clickable" probe, PIK-BPyne, to assess activity of PIKs in native biological systems and demonstrated its ability to monitor hepatitis C virus-induced changes in PIK-IIIβ activity.
Publication date	2014
In	ChemBioChem 15, no. 9 (2014): 1253–1256.
Language	English
Peer reviewed	Yes
NPARC number	21272798
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Record identifier	4f44d72f-257a-4b1e-b423-346b838f0840
Record created	2014-12-03
Record modified	2020-04-22

Date modified:: 2024-07-17