Classes of phosphoinositide 3-kinases at a glance

Jean, Steve; Kiger, Amy A.

doi:10.1242/jcs.093773

Cited by 281 publications

(238 citation statements)

References 80 publications

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“…The class III PI3-kinases are ubiquitously present in all eukaryotes, and are pivotal to cell division and survival, intracellular signaling, membrane dynamics and cell motility, adhesion, and differentiation (13,14). Specifically, they have been implicated in the regulation of mitogenic signaling, endosome to Golgi trafficking, vacuolar protein sorting, polarized endocytic sorting, phagosome maturation, and autophagy (14,15).…”

mentioning

confidence: 99%

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata

Sharma

Purushotham

Kaur

2016

Journal of Biological Chemistry

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Edited by James SiedowThe phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol and produces PI3P, has been implicated in protein trafficking, intracellular survival, and virulence in the pathogenic yeast Candida glabrata. Here, we demonstrate PI3-kinase (CgVps34) to be essential for maintenance of cellular iron homeostasis. We examine how CgVps34 regulates the fundamental process of iron acquisition, and underscore its function in vesicular trafficking as a central determinant. RNA sequencing analysis revealed iron homeostasis genes to be differentially expressed upon CgVps34 disruption. Consistently, the Cgvps34⌬ mutant displayed growth attenuation in low-and high-iron media, increased intracellular iron content, elevated mitochondrial aconitase activity, impaired biofilm formation, and extenuated mouse organ colonization potential. Furthermore, we demonstrate for the first time that C. glabrata cells respond to iron limitation by expressing the iron permease CgFtr1 primarily on the cell membrane, and to iron excess via internalization of the plasma membrane-localized CgFtr1 to the vacuole. Our data show that CgVps34 is essential for the latter process. We also report that macrophage-internalized C. glabrata cells express CgFtr1 on the cell membrane indicative of an iron-restricted macrophage internal milieu, and Cgvps34⌬ cells display better survival in iron-enriched medium-cultured macrophages. Overall, our data reveal the centrality of PI3K signaling in iron metabolism and host colonization.

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mentioning

confidence: 99%

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata

Sharma

Purushotham

Kaur

2016

Journal of Biological Chemistry

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“…PI3K is a family of lipid kinases that phosphorylate the 3'-position hydroxyl of the D-myo-inositol head group to generate specific phosphoinositide forms [103] . Based on their in vitro lipid substrate specificity, structure, and mode of regulation, PI3Ks can be divided into three main classes.…”

Section: Ataxia Telangiectasia-mutated C-abl and Phosphatidylinositimentioning

confidence: 99%

“…Based on their in vitro lipid substrate specificity, structure, and mode of regulation, PI3Ks can be divided into three main classes. [103] . It is a heterodimer composed of a p110 catalytic subunit and a p85 regulatory subunit [103] .…”

Section: Ataxia Telangiectasia-mutated C-abl and Phosphatidylinositimentioning

confidence: 99%

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How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5?

Zhou

2016

WJN

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NFAT5 plays a critical role in maintaining the renal functions. Its dis-regulation in the kidney leads to or is associated with certain renal diseases or disorders, most notably the urinary concentration defect. Hypertonicity, which the kidney medulla is normally exposed to, activates NFAT5 through phosphorylation of a signaling molecule or NFAT5 itself. Hypotonicity inhibits NFAT5 through a similar mechanism. More than a dozen of protein and lipid kinases have been identified to contribute to tonicity-dependent regulation of NFAT5. Hypertonicity activates NFAT5 by increasing its nuclear localization and transactivating activity in the early phase and protein abundance in the late phase. The known mechanism for inhibition of NFAT5 by hypotonicity is a decrease of nuclear NFAT5. The present article reviews the effect of each kinase on NFAT5 nuclear localization, transactivation and protein abundance, and the relationship among these kinases, if known. Cyclosporine A and tacrolimus suppress immune reactions by inhibiting the phosphatase calcineurin-dependent activation of NFAT1. It is hoped that this review would stimulate the interest to seek explanations from the NFAT5 regulatory pathways for certain clinical presentations and to explore novel therapeutic approaches based on the pathways. On the basic science front, this review raises two interesting questions. The first one is how these kinases can specifically signal to NFAT5 in the context of hypertonicity or hypotonicity, because they also regulate other cellular activities and even opposite activities in some cases. The second one is why these many kinases, some of which might have redundant functions, are needed to regulate NFAT5 activity. This review reiterates the concept of signaling through cooperation. Cells need these kinases working in a coordinated way to provide the signaling specificity that is lacking in the individual one. Redundancy in regulation of NFAT5 is a critical strategy for cells to maintain robustness against hypertonic or hypotonic stress. Core tip: NFAT5 is critical for kidney functions. Its disregulation results in or is associated with the renal diseases and disorders. More than a dozen of kinases have been identified to contribute to tonicity-dependent regulation of NFAT5. The present review is focused on how these kinases regulate NFAT5 activity under the context of hypertonicity or hypotonicity. Understanding these regulatory mechanisms will have therapeutic implications. A precedent example is that recognition of the cyclosporine immunosuppressive effect resulted from inhibition of the phosphatase calcineurin-dependent activation of NFAT1 allows combination use of cyclosporine with other mechanistically different immunosuppressants to improve their therapeutic efficacy and reduce their side effects.Zhou X. How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5? World J Nephrol 2016; 5(1): 20-32 Available from:

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“…PIP2 and PIP3 are phospholipids located in the plasma membrane that act as substrates for various signaling proteins. These phosphoinositide lipids play important roles in various processes such as cell signaling, lipid signaling, and membrane trafficking (Jean and Kiger, 2014).…”

Section: Pka Pathway In U Maydismentioning

confidence: 99%

Examination of the relevance of PI3K and PTEN pathway in Ustilago maydis.

Dalton¹

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Classes of phosphoinositide 3-kinases at a glance

Cited by 281 publications

References 80 publications

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata

How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5?

Examination of the relevance of PI3K and PTEN pathway in Ustilago maydis.

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