Class I PI 3-kinases: Function and evolution

Kriplani, Nisha; Hermida, Miguel A.; Brown, Euan R.; Leslie, Nicholas R.

doi:10.1016/j.jbior.2015.05.002

Cited by 69 publications

(40 citation statements)

References 101 publications

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“…PIP3 serves to target a variety of proteins to the membrane. PIP3 recruits Akt Kinase, which can inhibit GSK3-β, and activate other signaling pathways such as mTOR (Pan et al, 2005; Quian et al, 2005; Toker and Marmiroli, 2014; Kriplani et al, 2015). The PI3K pathway is a major regulator of axonal growth, controlling cellular cytoskeletal dynamics and expression of genes functioning during neuron morphogenesis (Atwal et al, 2000; Arévalo et al, 2006; Cosker and Eickholt, 2007; Eickholt, et al 2007).…”

Section: Signaling Mechanisms That Regulate Cytoskeletal Dynamics Durmentioning

confidence: 99%

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches

Armijo-Weingart

Gallo

2017

Molecular and Cellular Neuroscience

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The formation of axon collateral branches from the pre-existing shafts of axons is an important aspect of neurodevelopment and the response of the nervous system to injury. This article provides an overview of the role of the cytoskeleton and signaling mechanisms in the formation of axon collateral branches. Both the actin filament and microtubule components of the cytoskeleton are required for the formation of axon branches. Recent work has begun to shed light on how these two elements of the cytoskeleton are integrated by proteins that functionally or physically link the cytoskeleton. While a number of signaling pathways have been determined as having a role in the formation of axon branches, the complexity of the downstream mechanisms and links to specific signaling pathways remain to be fully determined. The regulation of intra-axonal protein synthesis and organelle function are also emerging as components of signal-induced axon branching. Although much has been learned in the last couple of decades about the mechanistic basis of axon branching we can look forward to continue elucidating this complex biological phenomenon with the aim of understanding how multiple signaling pathways, cytoskeletal regulators and organelles are coordinated locally along the axon to give rise to a branch.

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Section: Signaling Mechanisms That Regulate Cytoskeletal Dynamics Durmentioning

confidence: 99%

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches

Armijo-Weingart

Gallo

2017

Molecular and Cellular Neuroscience

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“…PI3Ks are major players in cellular functions, where they contribute to a variety of cellular processes, including proliferation, survival, adhesion, and migration. 42 Interaction between the PI3 kinase and the EGF receptors is required for its activation, and it is mediated by association of the phosphorylated receptors with the p85 subunit of PI3K. 43 PI3Ks convert phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3).…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

Graphene Enhances Cellular Proliferation through Activating the Epidermal Growth Factor Receptor

Liu

Sun

Liao

et al. 2016

J. Agric. Food Chem.

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Graphene has promising applications in food packaging, water purification, and detective sensors for contamination monitoring. However, the biological effects of graphene are not fully understood. It is necessary to clarify the potential risks of graphene exposure to humans through diverse routes, such as foods. In the present study, graphene, as the model nanomaterial, was used to test its potential effects on the cell proliferation based on multiple representative cell lines, including HepG2, A549, MCF-7, and HeLa cells. Graphene was characterized by Raman spectroscopy, particle size analysis, atomic force microscopy, and transmission electron microscopy. The cellular responses to graphene exposure were evaluated using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and alamarBlue assays. Rat cerebral astrocyte cultures, as the non-cancer cells, were used to assess the potential cytotoxicity of graphene as well. The results showed that graphene stimulation enhanced cell proliferation in all tested cell cultures and the highest elevation in cell growth was up to 60%. A western blot assay showed that the expression of epidermal growth factor (EGF) was upregulated upon graphene treatment. The phosphorylation of EGF receptor (EGFR) and the downstream proteins, ShC and extracellular regulating kinase (ERK), were remarkably induced, indicating that the activation of the mitogen-activated protein kinase (MAPK)/ERK signaling pathway was triggered. The activation of PI3 kinase p85 and AKT showed that the PI3K/AKT signaling pathway was also involved in graphene-induced cell proliferation, causing the increase of cell ratios in the G2/M phase. No influences on cell apoptosis were observed in graphene-treated cells when compared to the negative controls, proving the low cytotoxicity of this emerging nanomaterial. The findings in this study revealed the potential cellular biological effect of graphene, which may give useful hints on its biosafety evaluation and the further exploration of the bioapplication.

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“…There are >200 human proteins with Pleckstrin Homology (PH) domains, augmented by additional phosphoinositide-binding-domain families (see below). However, very few proteins in these families have been shown to preferentially bind PIP 3 , and protein homology has proven insufficient to identify PIP 3 -specific binding [4]. In contrast, structural analysis has shown promise for predicting PH-domain binding preferences [5].…”

Section: Introductionmentioning

confidence: 99%

“…Proteins with reported specificity for PIP 3 include the serine/threonine kinases AKT and PDK-1 [4]; Phospholipase C (PLC) isoforms [16]; atypical protein kinase C, aPKC (e.g., Mζ and ι / λ isoforms) [17]; cytohesins [4]; general receptor for phosphoinositides 1, GRP1 [18]; kindlin3 [19]; IL-2 inducible T-cell kinase, ITK [20]; Skap-hom [21]; and Arf GTPase-activating protein 1 [4, 22]. Protein domains reported to confer PIP 3 -specific binding in some proteins (although based on quite variable evidence) include pleckstrin homology (PH) domains [4], Phox-homology (PX) and FYVE domains [23, 24], P2X domains [25], and the SYLF domain [26].…”

Section: Introductionmentioning

confidence: 99%

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PIP3-binding proteins promote age-dependent protein aggregation and limit survival inC. elegans

et al. 2016

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Class-I phosphatidylinositol 3-kinase (PI3KI) converts phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-triphosphate (PIP3). PIP3 comprises two fatty-acid chains that embed in lipid-bilayer membranes, joined by glycerol to inositol triphosphate. Proteins with domains that specifically bind that head-group (e.g. pleckstrin-homology [PH] domains) are thus tethered to the inner plasma-membrane surface where they have an enhanced likelihood of interaction with other PIP3-bound proteins, in particular other components of their signaling pathways. Null alleles of the C. elegans age-1 gene, encoding the catalytic subunit of PI3KI, lack any detectable class-I PI3K activity and so cannot form PIP3. These mutant worms survive almost 10-fold longer than the longest-lived normal control, and are highly resistant to a variety of stresses including oxidative and electrophilic challenges. Traits associated with age-1 mutation are widely believed to be mediated through AKT-1, which requires PIP3 for both tethering and activation. Active AKT complex phosphorylates and thereby inactivates the DAF-16/FOXO transcription factor. However, extensive evidence indicates that pleiotropic effects of age-1-null mutations, including extreme longevity, cannot be explained by insulin like-receptor/AKT/FOXO signaling alone, suggesting involvement of other PIP3-binding proteins. We used ligand-affinity capture to identify membrane-bound proteins downstream of PI3KI that preferentially bind PIP3. Computer modeling supports a subset of candidate proteins predicted to directly bind PIP3 in preference to PIP2, and functional testing by RNAi knockdown confirmed candidates that partially mediate the stress-survival, aggregation-reducing and longevity benefits of PI3KI disruption. PIP3-specific candidate sets are highly enriched for proteins previously reported to affect translation, stress responses, lifespan, proteostasis, and lipid transport.

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Class I PI 3-kinases: Function and evolution

Cited by 69 publications

References 101 publications

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches

Graphene Enhances Cellular Proliferation through Activating the Epidermal Growth Factor Receptor

PIP3-binding proteins promote age-dependent protein aggregation and limit survival inC. elegans

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