Diphosphoinositol polyphosphates: What are the mechanisms?

Shears, Stephen B.; Gokhale, Nikhil A.; Wang, Huanchen; Zaremba, Angelika

doi:10.1016/j.advenzreg.2010.09.008

Cited by 26 publications

(37 citation statements)

References 94 publications

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“…We should clarify that the importance of InsP 6 stems both from its own role and as a platform from which other regulatory molecules are derived. Examples of the latter include the inositol pyrophosphates (Barker et al, 2009b;Shears et al, 2011;Saiardi, 2012) (see section IV) or the Ins(1,2,3)P 3 -based inositol polyphosphates with iron-binding properties (Barker et al, 1995;Spiers et al, 1996;Irvine, 2005). In terms of the direct effects of the molecule, two or three different modes of operation for InsP 6 can be identified.…”

Section: Novel Roles Of Insp 6 Outside the B-cellmentioning

confidence: 99%

“…One of the important and exciting new frontiers in the inositol polyphosphate field has been the growing revelation that inositol pyrophosphates serve as critical regulators in many cell systems (Barker et al, 2009b;Chakraborty et al, 2011;Shears et al, 2011;Saiardi, 2012). Again, the pancreatic b-cell has provided an important platform for discovering the physiologic relevance of this novel inositide family (Barker et al, 2009a).…”

Section: Inositol Pyrophosphatesmentioning

confidence: 99%

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New Horizons in Cellular Regulation by Inositol Polyphosphates: Insights from the Pancreaticβ-Cell

Barker

Berggren

2013

Pharmacol Rev

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Section: Novel Roles Of Insp 6 Outside the B-cellmentioning

confidence: 99%

Section: Inositol Pyrophosphatesmentioning

confidence: 99%

New Horizons in Cellular Regulation by Inositol Polyphosphates: Insights from the Pancreaticβ-Cell

Barker

Berggren

2013

Pharmacol Rev

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“…2,3 In the early 1990s, a distinct subclass of inositol polyphosphates containing 'high energy' pyrophosphate groups was identified in slime mould and mammalian cells. [4][5][6] Since then several studies have characterized these inositol pyrophosphates (PP-IPs) and their functions (for Akruti Shah 1,2 , Shubhra Ganguli 1,2 , Jayraj Sen 1,2 and Rashna Bhandari reviews see 2,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] ). The major PP-IPs, diphosphoinositol pentakisphosphate, PP-IP 5 (or IP 7 ) and bis-diphosphoinositol tetrakisphosphate, [PP] 2 -IP 4 (or IP 8 ), are derived by the addition of phosphate groups to pre-existing monophosphates on IP 6 (Fig.…”

Section: Introductionmentioning

confidence: 99%

Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules

et al. 2017

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| Inositol pyrophosphates (PP-IPs) are a class of energy-rich signalling molecules found in all eukaryotic cells. These are derivatives of inositol that contain one or more diphosphate (or pyrophosphate) groups in addition to monophosphates. The more abundant and best studied PP-IPs are diphosphoinositol pentakisphosphate (IP 7 ) and bis-diphosphoinositol tetrakisphosphate (IP 8 ). These molecules can influence protein function by two mechanisms: binding and pyrophosphorylation. The former involves the specific interaction of a particular inositol pyrophosphate with a binding site on a protein, while the latter is a unique attribute of inositol pyrophosphates, wherein the β-phosphate moiety is transferred from a PP-IP to a pre-phosphorylated serine residue in a protein to generate pyrophosphoserine. Both these events can result in changes in the target protein's activity, localisation or its interaction with other partners. As a consequence of their ubiquitous presence in all eukaryotic organisms and all cell types examined till date, and their ability to modify protein function, PP-IPs have been found to participate in a wide range of metabolic, developmental, and signalling pathways.This review highlights many of the known functions of PP-IPs in the context of their temporal and spatial distribution in eukaryotic cells. The pathway of synthesis of inositol polyphosphates has been characterized in yeast, slime moulds, plants and animals. The simplest anabolic pathway, characterized in the yeast Saccharomyces cerevisiae (Fig. 1) (Fig. 1). Interestingly, the PPIP5Ks also possess a phosphatase domain which selectively cleaves the 1-position β-phosphate of 1-IP 7 and IP 8 , thus targeting the products of the kinase domain.35, 36 A recent study identified another yeast phosphatase, Siw14, that specifically targets the 5-position β-phosphate of PP-IPs 37 (Fig. 1). As PP-IPs are found in all eukaryotic organisms, they display many conserved and divergent 2, 131 Siw14, an inositol pyrophosphate phosphatase in yeast, preferentially cleaves the C5 β-phosphate on PP-IPs. 37 The yeast enzymes are depicted in purple, and mammalian enzymes are depicted in green and are bracketed. The undetermined inositol pyrophosphate structure is represented with an interrogation mark. Myoinositol contains five equatorial (parallel to the axis) and one axial (perpendicular to the axis) hydroxyl groups. Carbon atoms on the myo-inositol ring are numbered on the structures of PI(4,5)P 2 and IP 6 .

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“…45 Khan et al showed that IL1RAPL can active c-Jun amino-terminal kinases (JNKs) but not extracellular signal-regulated kinases (ERKs) nor mitogen-activated protein kinases (MAPKs). 46 Although IL1R have high affinities for their ligands, the accessory proteins cannot do it directly. Furthermore, the function of IL1RAPL might be more related to the Toll-like receptors subfamily than IL1R subfamily.…”

Section: Discussionmentioning

confidence: 99%

“…This gene belongs to NUDT gene family (NUDT = 'Nudix [Nucleoside Diphosphate attached moiety 'x']-Type motif) and encode a phosphatase involved in the diphosphoinositol polyphosphates cell turnover. 46 The diphosphoinositol polyphosphates have been implicated in several cellular activities, such as homolog recombination, vesicle trafficking, apoptosis and response to environmental stress. [47][48][49] Although association of the NUDT genes with asthma has not been previously reported, the diphosphoinositol polyphosphates syntheses is activated in cells subjected to stress by hyperosmotic pressure.…”

Section: Discussionmentioning

confidence: 99%

Suggestive association between variants in IL1RAPL and asthma symptoms in Latin American children

et al. 2017

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Several genome-wide association studies have been conducted to investigate the influence of genetic polymorphisms in the development of allergic diseases, but few of them have included the X chromosome. The aim of present study was to perform an X chromosome-wide association study (X-WAS) for asthma symptoms. The study included 1307 children of which 294 were asthma cases. DNA was genotyped using 2.5 HumanOmni Beadchip from Illumina. Statistical analyses were performed in PLINK 1.9, MACH 1.0 and Minimac2. The variant rs12007907 (g.29483892C4A) in IL1RAPL gene was suggestively associated with asthma symptoms in discovery set (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.37-0.67; P = 3.33 × 10 −6 ). This result was replicated in the ProAr cohort in men only (OR = 0.45, 95% CI: 0.21-0.95; P = 0.038). Furthermore, investigating the functional role of the rs12007907 on the production a Th2-type cytokine, IL-13, we found a negative association between the minor allele A with IL-13 production in the discovery set (P = 0.044). Gene-based analysis revealed that NUDT10 was the most consistently associated with asthma symptoms in discovery sample. In conclusion, the rs12007907 variant in IL1RAPL gene was negatively associated with asthma and IL-13 production in our study and a sex-specific association was observed in one of the validation samples. It suggests an effect on asthma susceptibility and may explain differences in severe asthma frequency between women and men.

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Diphosphoinositol polyphosphates: What are the mechanisms?

Cited by 26 publications

References 94 publications

New Horizons in Cellular Regulation by Inositol Polyphosphates: Insights from the Pancreaticβ-Cell

New Horizons in Cellular Regulation by Inositol Polyphosphates: Insights from the Pancreaticβ-Cell

Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules

Suggestive association between variants in IL1RAPL and asthma symptoms in Latin American children

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