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Updated: Jun 21, 2026

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
Published on: January 6, 2016
Form and flexibility in phosphoinositide 3-kinases
Roger Williams1, Alex Berndt, Simon Miller
1MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. rlw@mrc-lmb.cam.ac.uk
Abstract:
PI3Ks (phosphoinositide 3-kinases) have important roles in a variety of cellular activities, including survival, proliferation, growth, shape, migration and intracellular sorting. Consistent with their function in cell survival and growth, the gene for the class Ialpha PI3K catalytic subunit is a common site of gain-of-function mutations in cancers. Ongoing structural studies of these enzymes and the complexes they make with their regulatory subunits have helped to clarify the mechanistic basis of this role in tumour development. The broad spectrum of biological activities associated with various isotypes of class I PI3Ks has led to an intense search for isotype-specific inhibitors as tools in mammalian cell biology and for therapeutic application. Structural studies of the class I PI3Ks suggest that flexibility may be a component of the catalytic cycle of the enzymes.
Insights
Phosphoinositide 3-kinases (PI3Ks) are crucial for cell survival and growth, with mutations linked to cancer. Understanding PI3K structure aids in developing targeted cancer therapies and cell biology tools.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Phosphoinositide 3-kinases (PI3Ks) regulate essential cellular processes like survival, proliferation, and migration.
- Gain-of-function mutations in PI3K genes are frequently observed in various cancers, highlighting their role in tumorigenesis.
Purpose of the Study:
- To elucidate the mechanistic basis of PI3K's role in cancer development through ongoing structural studies.
- To identify and develop isotype-specific PI3K inhibitors for applications in cell biology and therapeutics.
Main Methods:
- Structural studies of PI3K enzymes and their regulatory subunit complexes.
- Analysis of PI3K's catalytic cycle and enzyme flexibility.
Main Results:
- Structural insights are clarifying the mechanistic underpinnings of PI3K's involvement in tumor development.
- The broad biological activities of PI3K isotypes necessitate the search for specific inhibitors.
Conclusions:
- Structural studies of PI3Ks are pivotal for understanding their oncogenic roles.
- Developing isotype-specific PI3K inhibitors is a key strategy for both research tools and cancer therapy.
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