Discovery of Molecular and Catalytic Diversity among Human Diphosphoinositol-Polyphosphate Phosphohydrolases

Caffrey, James L.; Safrany, Stephen T.; Yang, Xiao; Shears, Stephen B.

doi:10.1074/jbc.275.17.12730

Cited by 90 publications

(111 citation statements)

References 31 publications

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“…To ensure that all of the inositol polyphosphate pools were radiolabeled to equilibrium, their saturation with [ 3 H]inositol during the time course of our experiments was ensured by labeling for at least eight cell generations. As shown previously (28,29), InsP 1 and InsP 6 account for more than 99% of the total spectrum of inositol phosphates in yeast cells (Fig. 2).…”

Section: The Effect Of Deletion Of the Kcs1 Gene Upon Dins Activity Asupporting

confidence: 82%

In Saccharomyces cerevisiae, the Inositol Polyphosphate Kinase Activity of Kcs1p Is Required for Resistance to Salt Stress, Cell Wall Integrity, and Vacuolar Morphogenesis

Dubois¹,

Scherens²,

Vierendeels³

et al. 2002

Journal of Biological Chemistry

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A problem for inositol signaling is to understand the significance of the kinases that convert inositol hexakisphosphate to diphosphoinositol polyphosphates. This kinase activity is catalyzed by Kcs1p in the yeast Saccharomyces cerevisiae. A kcs1⌬ yeast strain that was transformed with a specifically "kinase-dead" kcs1p mutant did not synthesize diphosphoinositol polyphosphates, and the cells contained a fragmented vacuolar compartment. Biogenesis of the yeast vacuole also required another functional domain in Kcs1p, which contains two leucine heptad repeats. The kinase activity of Kcs1p was also found to sustain cell growth and integrity of the cell wall and to promote adaptive responses to salt stress. Thus, the synthesis of diphosphoinositol polyphosphates has wide ranging physiological significance. Furthermore, we showed that these phenotypic responses to Kcs1p deletion also arise when synthesis of precursor material for the diphosphoinositol polyphosphates is blocked in arg82⌬ cells. This metabolic block was partially bypassed, and the phenotype was partially rescued, when Kcs1p was overexpressed in the arg82⌬ cells. This was due, in part, to the ability of Kcs1p to phosphorylate a wider range of substrates than previously appreciated. Our results show that diphosphoinositol polyphosphate synthase activity is essential for biogenesis of the yeast vacuole and the cell's responses to certain environmental stresses.

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Section: The Effect Of Deletion Of the Kcs1 Gene Upon Dins Activity Asupporting

confidence: 82%

In Saccharomyces cerevisiae, the Inositol Polyphosphate Kinase Activity of Kcs1p Is Required for Resistance to Salt Stress, Cell Wall Integrity, and Vacuolar Morphogenesis

Dubois¹,

Scherens²,

Vierendeels³

et al. 2002

Journal of Biological Chemistry

Self Cite

112

145

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“…IP 8 is generated via the combined action of the IP6Ks and PPIP5Ks (Wang et al 2012). The de-phosphorylation of inositol pyrophosphates to IP 6 or IP 5 is catalyzed by the enzyme diphosphoinositol polyphosphate phosphohydrolase (DIPP) (Safrany and Shears 1998;Safrany et al 1999;Caffrey et al 2000;Kilari et al 2013) (Figure 1). Compared to 5-IP 7 , 1-IP 7 seems to be a better substrate for DIPP (Lonetti et al 2011;Kilari et al 2013).…”

Section: Biosynthesis Of the Inositol Pyrophosphatesmentioning

confidence: 99%

Inositol pyrophosphates as multifaceted metabolites in the regulation of mammalian signaling networks

Park

Lee

Kim

2017

Animal Cells and Systems

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Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP 7 ) are inositol metabolites with high-energy phosphoanhydride bonds. The formation of PP-IPs is catalyzed by two groups of enzymes, the IP6 kinases and the PPIP5 kinases, which both phosphorylate inositol hexakisphosphate (IP 6 ). In mammals, PP-IPs are implicated in diverse biological phenomena including cellular growth, vesicular trafficking, apoptosis, and metabolic homeostasis. Mechanistically, all the diverse actions of PP-IPs proceed in one of two ways: the PP-IPs modulate the activity of their target proteins either through allosteric binding or protein pyrophosphorylation. In this review, we highlight recent advances in our understanding of the pleiotropic functions of the mammalian PP-IPs and the metabolic enzymes that produce them. We also discuss some future challenges in the exploration of areas where PP-IPs play important but unknown roles in physiology and disease.ARTICLE HISTORY

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“…All IP6 kinases also phosphorylate IP5 to PP-IP4 (12). Not shown is the hydrolysis of the diester phosphates by specific phosphohydrolases (19). So, what don't we know?…”

Section: Regulation Of Telomere Lengthmentioning

confidence: 99%

Telomere maintenance by intracellular signals: New kid on the block?

Shears¹

2005

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

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Discovery of Molecular and Catalytic Diversity among Human Diphosphoinositol-Polyphosphate Phosphohydrolases

Cited by 90 publications

References 31 publications

In Saccharomyces cerevisiae, the Inositol Polyphosphate Kinase Activity of Kcs1p Is Required for Resistance to Salt Stress, Cell Wall Integrity, and Vacuolar Morphogenesis

In Saccharomyces cerevisiae, the Inositol Polyphosphate Kinase Activity of Kcs1p Is Required for Resistance to Salt Stress, Cell Wall Integrity, and Vacuolar Morphogenesis

Inositol pyrophosphates as multifaceted metabolites in the regulation of mammalian signaling networks

Telomere maintenance by intracellular signals: New kid on the block?

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