Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling

Prasad, Amit; Jia, Yonghui; Chakraborty, Anutosh; Li, Yitang; Jain, Supriya; Zhong, Jia; Roy, Saurabh G.; Loison, Fabien; Mondal, Subhanjan; Sakai, Jiro; Blanchard, Catlyn; Snyder, Solomon H.; Luo, Hongbo

doi:10.1038/ni.2052

Cited by 78 publications

(108 citation statements)

References 50 publications

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“…death (16). It appears that disruption of InsP6K1 does not affect Akt activation in aging neutrophils (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…There is substantial InsP7 in unstimulated cells, which prevents neutrophil hyperactivation and ensures an optimal cellular inflammatory response. The cellular concentration of InsP7 rapidly decreases after stimulation with chemoattractants, which allows the induction of sustained PtdIns(3,4,5)P3 signal in responding neutrophils (16). Reducing InsP7 production via InsP6K1 disruption augments chemoattractant-elicited PtdIns(3,4,5)P3 signaling in neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…InsP6K1 seems to be equally distributed in the nucleus and cytoplasm, whereas InsP6K2 appears to be almost exclusively nuclear (20). In a recent study, we reported that PtdIns (3,4,5)P3/Akt signaling in neutrophils is mainly regulated by InsP6K1 (16). To further investigate the role of InsP7 in regulating PtdIns(3,4,5)P3 signaling in neutrophil spontaneous death, we elevated the intracellular level of InsP7 by overexpressing InsP6K1 in HL60 cells, in which specific genes can be easily overexpressed (Fig.…”

Section: Insp6k1-mediated Insp7 Production Is a Key Mediator Of Cse-andmentioning

confidence: 99%

“…S2). Interestingly, a significant amount of InsP7 was detected in unstimulated neutrophils (16). Treatment with CSE or nicotine reduced InsP7 levels in neutrophils (Fig.…”

Section: Effects Of Cse and Nicotine On Neutrophil Spontaneous Death mentioning

confidence: 99%

“…All procedures involving mice were approved and monitored by the Children's Hospital Boston Institutional Animal Care and Use Committee. InsP6k1 −/− mice were generated as described (16). The corresponding WT littermates were used as paired controls for InsP6k1 −/− mice.…”

Section: Methodsmentioning

confidence: 99%

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Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate

Bajrami

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Diphosphoinositol pentakisphosphate (InsP7), a higher inositol phosphate containing energetic pyrophosphate bonds, is beginning to emerge as a key cellular signaling molecule. However, the various physiological and pathological processes that involve InsP7 are not completely understood. Here we report that cigarette smoke (CS) extract and nicotine reduce InsP7 levels in aging neutrophils. This subsequently leads to suppression of Akt deactivation, a causal mediator of neutrophil spontaneous death, and delayed neutrophil death. The effect of CS extract and nicotine on neutrophil death can be suppressed by either directly inhibiting the PtdIns(3,4,5)P3/Akt pathway, or increasing InsP7 levels via overexpression of InsP6K1, an inositol hexakisphosphate (InsP6) kinase responsible for InsP7 production in neutrophils. Delayed neutrophil death contributes to the pathogenesis of CS-induced chronic obstructive pulmonary disease. Therefore, disruption of InsP6K1 augments CS-induced neutrophil accumulation and lung damage. Taken together, these results suggest that CS and nicotine delay neutrophil spontaneous death by suppressing InsP7 production and consequently blocking Akt deactivation in aging neutrophils. Modifying neutrophil death via this pathway provides a strategy and therapeutic target for the treatment of tobacco-induced chronic obstructive pulmonary disease.

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“…death (16). It appears that disruption of InsP6K1 does not affect Akt activation in aging neutrophils (Fig.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Insp6k1-mediated Insp7 Production Is a Key Mediator Of Cse-andmentioning

confidence: 99%

“…S2). Interestingly, a significant amount of InsP7 was detected in unstimulated neutrophils (16). Treatment with CSE or nicotine reduced InsP7 levels in neutrophils (Fig.…”

Section: Effects Of Cse and Nicotine On Neutrophil Spontaneous Death mentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate

Bajrami

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Synthesis of Densely Phosphorylated Bis‐1,5‐Diphospho‐myo‐Inositol Tetrakisphosphate and its Enantiomer by Bidirectional P‐Anhydride Formation

et al. 2014

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The ubiquitous mammalian signaling molecule bisdiphosphoinositol tetrakisphosphate (1,5-(PP) 2 -myo-InsP 4 , or InsP 8 ) displays the most congested three-dimensional array of phosphate groups found in nature. The high charge density, the accumulation of unstable P-anhydrides and P-esters, the lack of UV absorbance, and low levels of optical rotation constitute severe obstacles to its synthesis, characterization, and purification. Herein, we describe the first procedure for the synthesis of enantiopure 1,5-(PP) 2 -myo-InsP 4 and 3,5-(PP) 2 -myo-InsP 4 utilizing a C 2 -symmetric P-amidite for desymmetrization and concomitant phosphitylation followed by a one-pot bidirectional P-anhydride-forming reaction that combines sixteen chemical transformations with high efficiency. The configuration of these materials is unambiguously shown by subsequent Xray analyses of both enantiomers after being individually soaked into crystals of the kinase domain of human diphosphoinositol pentakisphosphate kinase 2.

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An Affinity Reagent for the Recognition of Pyrophosphorylated Peptides

Conway

Fiedler

2015

Angewandte Chemie

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A resin‐bound dinuclear zinc(II) complex for the selective capture of pyrophosphopeptides is reported. The metal complex binds diphosphate esters over other anionic groups, such as monophosphate esters, sulfate esters, and carboxylic acids, with high specificity. Immobilization of the compound provided a reagent capable of binding and retaining nanomolar quantities of pyrophosphopeptide in the presence of cell lysate. The high affinity and specificity of the reagent makes it an attractive tool for the study of in vivo pyrophosphorylation.

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Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling

Cited by 78 publications

References 50 publications

Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate

Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate

Synthesis of Densely Phosphorylated Bis‐1,5‐Diphospho‐myo‐Inositol Tetrakisphosphate and its Enantiomer by Bidirectional P‐Anhydride Formation

An Affinity Reagent for the Recognition of Pyrophosphorylated Peptides

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