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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Extracellular and subcellular regulation of the PI3K/Akt cassette: new mechanisms for controlling insulin and growth
C Wilson1, N Vereshchagina, B Reynolds
1Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, UK. clive.wilson@dpag.ox.ac.uk
Abstract:
The PI3K (phosphoinositide 3-kinase)/Akt (also called protein kinase B) signalling cassette plays a central role in the response to growth factors, particularly insulin-like molecules, and its misregulation is a characteristic feature of diabetes and many forms of human cancer. Recent molecular genetic studies initiated in the fruitfly, Drosophila melanogaster, have highlighted two new cell-type-specific mechanisms regulating PI3K/Akt signalling and its downstream effects. First, the cellular response to this cassette is modulated by several classes of cell-surface transporters and sensors, suggesting an important role for extracellular nutrients in insulin-sensitivity. Secondly, various cell types show a markedly different subcellular distribution of the activated kinase Akt, influencing the cellular functions of this molecule. These findings reveal new mechanisms by which processes such as growth, lipogenesis and insulin resistance can be differentially regulated and may suggest novel strategies for treating insulin-linked diseases.
Insights
New fruitfly studies reveal nutrient transporters and Akt kinase distribution regulate phosphoinositide 3-kinase/Akt signaling. These findings offer insights into insulin resistance and potential treatments for linked diseases.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is crucial for cellular responses to growth factors, especially insulin-like molecules.
- Dysregulation of PI3K/Akt signaling is implicated in diabetes and various human cancers.
Purpose of the Study:
- To identify novel mechanisms regulating PI3K/Akt signaling using molecular genetic studies in Drosophila melanogaster.
- To explore the influence of extracellular nutrients and subcellular Akt distribution on PI3K/Akt pathway activity.
Main Methods:
- Molecular genetic analysis in Drosophila melanogaster.
- Investigation of cell-surface transporters and sensors.
- Analysis of subcellular localization of activated Akt kinase.
Main Results:
- Cell-surface transporters and sensors modulate cellular responses to PI3K/Akt signaling, highlighting the role of extracellular nutrients in insulin sensitivity.
- Different cell types exhibit distinct subcellular distributions of activated Akt, impacting its cellular functions.
- Two novel cell-type-specific regulatory mechanisms of PI3K/Akt signaling were identified.
Conclusions:
- Extracellular nutrients and the subcellular localization of Akt kinase are key regulators of PI3K/Akt signaling.
- These findings provide new insights into the differential regulation of growth, lipogenesis, and insulin resistance.
- The identified mechanisms may suggest novel therapeutic strategies for insulin-related diseases.
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