GSK3 and its interactions with the PI3K/AKT/mTOR signalling network
Miguel A Hermida1, J Dinesh Kumar1, Nick R Leslie1
1Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot Watt University, Edinburgh EH14 4AS, UK.
Advances in Biological Regulation
|July 18, 2017
Summary
Glycogen Synthase Kinase-3 (GSK3) is a key kinase in cell metabolism and neuroscience. Its regulation is complex, involving independent pools and priming phosphorylation events, and it integrates with the PI3K-AKT-mTOR pathway.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Signaling
Background:
- Glycogen Synthase Kinase-3 (GSK3) is a promiscuous kinase impacting physiology and pathology.
- GSK3 is a substrate of AKT, with AKT-mediated phosphorylation inhibiting GSK3 activity.
- GSK3 integrates with the PI3K/AKT/mTOR signaling network, influencing cellular metabolism, lineage commitment, and neuroscience.
Purpose of the Study:
- To discuss the diverse aspects of GSK3 regulation and function.
- To explore GSK3's integration with the PI3K-AKT-mTOR signaling axis.
- To highlight GSK3's role as an amplifier of priming phosphorylation events.
Main Methods:
- Literature review and synthesis of existing research on GSK3.
- Analysis of GSK3's interactions within the PI3K/AKT/mTOR pathway.
- Discussion of substrate-specific regulation mechanisms, including priming phosphorylation.
Main Results:
- GSK3 exhibits functionally distinct, independently regulated pools.
- Regulation of GSK3 activity is often controlled by priming phosphorylation events specific to substrates.
- GSK3 phosphorylates multiple components of the PI3K/AKT/mTOR network, suggesting feedback control.
Conclusions:
- GSK3 plays a critical role in integrating signals within the PI3K-AKT-mTOR pathway.
- Substrate-specific priming phosphorylation is a major regulatory mechanism for GSK3.
- Understanding GSK3's complex regulation is crucial for its role in physiology and pathology.
More Related Videos
08:04Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
19.9K
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
18.8K
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
5.8K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.8K
01:20The JAK-STAT Signaling Pathway
13.4K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
13.4K
03:03mTOR Signaling and Cancer Progression
4.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.9K
01:19Interactions Between Signaling Pathways
7.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
01:22Amplifying Signals via Enzymatic Cascade
18.7K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
18.7K
01:07MAPK Signaling Cascades
8.8K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
8.8K