DOI: 10.1091/mbc.e08-05-0449. Spatiotemporal Analysis of Differential Akt Regulation in Plasma Membrane Microdomains

Spatiotemporal Analysis of Differential Akt Regulation in Plasma Membrane Microdomains

10.1091/mbc.e08-05-0449

Crossref journal-article

American Society for Cell Biology (ASCB)

Molecular Biology of the Cell (1076)

Abstract

As a central kinase in the phosphatidylinositol 3-kinase pathway, Akt has been the subject of extensive research; yet, spatiotemporal regulation of Akt in different membrane microdomains remains largely unknown. To examine dynamic Akt activity in membrane microdomains in living cells, we developed a specific and sensitive fluorescence resonance energy transfer-based Akt activity reporter, AktAR, through systematic testing of different substrates and fluorescent proteins. Targeted AktAR reported higher Akt activity with faster activation kinetics within lipid rafts compared with nonraft regions of plasma membrane. Disruption of rafts attenuated platelet-derived growth factor (PDGF)-stimulated Akt activity in rafts without affecting that in nonraft regions. However, in insulin-like growth factor-1 (IGF)-1 stimulation, Akt signaling in nonraft regions is dependent on that in raft regions. As a result, cholesterol depletion diminishes Akt activity in both regions. Thus, Akt activities are differentially regulated in different membrane microdomains, and the overall activity of this oncogenic pathway is dependent on raft function. Given the increased abundance of lipid rafts in some cancer cells, the distinct Akt-activating characteristics of PDGF and IGF-1, in terms of both effectiveness and raft dependence, demonstrate the capabilities of different growth factor signaling pathways to transduce differential oncogenic signals across plasma membrane.

Bibliography

Gao, X., & Zhang, J. (2008). Spatiotemporal Analysis of Differential Akt Regulation in Plasma Membrane Microdomains. Molecular Biology of the Cell, 19(10), 4366â4373.

Authors 2

Xinxin Gao (first)
Jin Zhang (additional)

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Dates

Type	When
Created	17 years ago (Aug. 13, 2008, 5:36 p.m.)
Deposited	6 years, 1 month ago (July 14, 2019, 7:16 a.m.)
Indexed	3 weeks, 2 days ago (Aug. 3, 2025, 12:09 a.m.)
Issued	16 years, 10 months ago (Oct. 1, 2008)
Published	16 years, 10 months ago (Oct. 1, 2008)
Published Print	16 years, 10 months ago (Oct. 1, 2008)

Funders 0

None

BibTeX

@article{Gao_2008, title={Spatiotemporal Analysis of Differential Akt Regulation in Plasma Membrane Microdomains}, volume={19}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e08-05-0449}, DOI={10.1091/mbc.e08-05-0449}, number={10}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Gao, Xinxin and Zhang, Jin}, editor={Schmid, Sandra L.}, year={2008}, month=oct, pages={4366–4373} }

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