Comparison of the levels of inositol metabolites in transformed haemopoietic cells and their normal counterparts

Bunce, Christopher M.; French, Philip J.; Allen, Patrick B.; Mountford, Joanne C.; Moor, B. C.; Greaves, Melvyn F.; Michell, Robert H.; Brown, Geoffrey

doi:10.1042/bj2890667

Cited by 86 publications

(78 citation statements)

References 31 publications

(22 reference statements)

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“…Conceivably, IP6 may modulate the oligomeric equilibrium of arrestin in rods to maintain a certain level of monomer to rapidly quench rhodopsin signaling. However, unless the concentration of IP6 in rod photoreceptors is much higher than in other cells (where it reaches up to 100 μM (34,35)), rods would contain a much higher concentration of arrestin than IP6, limiting the possible impact of IP6 on rod arrestin self-association status. On the other hand, since the concentration of rod arrestin is so high in photoreceptors (>1 mM) (23)(24)(25), its binding to IP6, even with relatively low affinity, might serve to scavenge free IP6, thereby reducing its concentration.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study by Milano et al also suggests that IP6 enhances the oligomerization of non-visual arrestins (32). Intracellular concentrations of IP6 are believed to range from 37 to 105 μM (34). Therefore, we tested the effect of IP6 directly by comparing the self-association of rod arrestin and arrestin2 in the presence and absence of 100 μM IP6.…”

Section: Ip6 Differentially Affects Rod Arrestin and Arrestin2 Self-amentioning

confidence: 99%

“…IP6 is the most abundant inositol polyphosphate in many cell types (reaching concentrations of 100 μM) (34,35). It is believed to play a role in numerous cellular events including receptor trafficking, neurotransmission, ion channel activation, mRNA export, etc.…”

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Opposing Effects of Inositol Hexakisphosphate on Rod Arrestin and Arrestin2 Self-Association

et al. 2007

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The robust cooperative formation of rod arrestin tetramers has been well-established, whereas the ability of other members of the arrestin family to self-associate remains controversial. Here, we used purified arrestins and multi-angle light scattering to quantitatively compare the propensity of the four mammalian arrestin subtypes to self-associate. Both non-visual and cone arrestins only form oligomers at very high non-physiological concentrations. However, inositol hexakisphosphate (IP6), a fairly abundant form of inositol in the cytoplasm, greatly facilitates self-association of arrestin2. Arrestin2 self-association equilibrium constants in the presence of 100 μM IP6 suggest that an appreciable proportion could exist in an oligomeric state but only in intracellular compartments where its concentration is 5-10-fold higher than average. In contrast to arrestin2, IP6 inhibits selfassociation of rod arrestin, indicating that the structure of these two tetramers in solution is likely different.Arrestins are multi-functional adaptor proteins that regulate signaling of G protein-coupled receptor (GPCR) 1 -dependent and -independent pathways. The first discovered and most studied function of arrestins is their ability to terminate GPCR signaling by preferentially binding the activated phosphorylated form of the receptor (reviewed in refs 1 and 2). There are four types of mammalian arrestins. The two subtypes expressed in photoreceptor cells, termed rod and cone arrestin, terminate rhodopsin and cone opsin signaling, respectively. The two non-visual subtypes, arrestins2 and -3 (i.e., β-arrestins1 and -2), are expressed ubiquitously and bind hundreds of different GPCRs (reviewed in ref 3). Arrestins also interact with numerous non-receptor binding partners including clathrin (4) and AP2 (5) to orchestrate intracellular trafficking of the arrestin-receptor complex, as well as members of the MAPK kinase cascades (cRaf, ERK1/2, ASK, and JNK3) (6-9), Src family kinases (10), the ubiquitin ligase Mdm2 (8,9,11,12), calmodulin (13), microtubules (14,15), and phosphoinositides (16-18).

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Section: Discussionmentioning

confidence: 99%

Section: Ip6 Differentially Affects Rod Arrestin and Arrestin2 Self-amentioning

confidence: 99%

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Opposing Effects of Inositol Hexakisphosphate on Rod Arrestin and Arrestin2 Self-Association

et al. 2007

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“…Thus, it is clear that concentrations of InsP 6 are high in some cells (30±100 mmol/L [4,5]), but it is unclear how much is freely soluble; certainly an important fraction of InsP 6 is not in solution because it is linked to cellular membranes [6]. Another important area of work is the synthetic pathway(s) of InsP 6 in vivo; thus, whereas in plant cells Ins(1,3,4,5,6)P 5 was identi®ed as the immediate precursor of InsP 6 [7,8], it remains uncertain whether a similar situation exists in animal cells.…”

Section: Introductionmentioning

confidence: 99%

Inositol hexakisphosphate in urine: the relationship between oral intake and urinary excretion

Gráses¹,

Simonet²,

March³

et al. 2000

BJU International

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Objective To study the relationship between the oral intake of inositol hexakisphosphate (InsP 6 , phytic acid, an inhibitor of urinary crystallization) and its urinary excretion, to establish their possible mutual in¯uence. Materials and methods Two groups of male Wistar rats (six animals each) received either; tap water and normal rat food pellets (controls); or a liquid diet in which InsP 6 was absent and which then received gradually increasing amounts of InsP 6 . The urinary levels of InsP 6 were then assessed regularly in both groups. Results When InsP 6 was absent from the diet, urinary excretion declined to undetectable levels after 22 days. The addition of increasing amounts of InsP 6 to the liquid diet caused an increase in its urinary excretion after about 10 days. Adding InsP 6 in amounts >425 mg/L caused no further increases in urinary excretion. Adding inositol (with no InsP 6 ) to the liquid diet caused only a slight increase in the urinary excretion of InsP 6 . Conclusion These results showed that InsP 6 urinary levels were related to its oral intake; consequently, a low consumption of InsP 6 would cause a urinary de®cit of this crystallization inhibitor and thus an increase in the risk of developing urinary calcium stones. Although urinary excretion was dose-dependent, there was an ingested amount (20.9 mg/kg) above which there was no increase in the amount excreted. This intake is easily obtained by consuming a normal diet (rich in InsP 6 ) indicating that to maintain appropriate urinary levels of InsP 6 , the consumption of InsP 6 supplements is only necessary when the diet is particularly poor in InsP 6 .

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“…Estimates of the total cellular concentration of InsP 6 range from 5 to 100 μΜ (130)(131)(132). This puts the levels of PP-InsP 5 and [PP] 2 -InsP 4 in the low micromolar range, at most.…”

Section: Diphosphorylated Inositidesmentioning

confidence: 99%

The Structural and Functional Versatility of Inositol Phosphates

Caffrey

Safrany

Yang

et al. 1998

ACS Symposium Series

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This review presents a summary of our current knowledge of inositol phosphate turnover in animal cells. In the Figure 1, the various metabolic reactions are sub-divided into several distinct groups; each of these is discussed in turn in this review, in an effort to illustrate the functional versatility of these polyphosphates.The Ins(l,4,5)P 3 / Ins(l,3,4,5)P 4 cycleThe discovery of inositol phosphate-mediated cellular Ca 2+ mobilization was a pivotal development in the field of signal transduction (/), but this breakthrough also owes much to the persistence of some other workers who had the foresight to develop and promote the idea of receptor-activated inositide signaling. It was the Hokins who first discovered that muscarinic agonists accelerate the turnover of Ptdlns in tissue slices from brain and pancreas (2). It was unfortunate that their dedication to characterizing this effect over the following 20 years did not lead them to ascribe its biological function. Indeed, there was little general interest in this so-called "phosphoinositide effect", until Michell (3) proposed that it might drive receptor-dependent Ca 2+ influx into the cell. Later, Michell and his colleagues showed mat an accelerated PtdIns(4,5)P 2 turnover immediately followed receptor-occupation by Ca 2+ -mobilizing hormones (4,5). The modem era of inositide research was now bom: Berridge (6) recognized that the Ins(l,4,5)P 3 formed by hydrolysis of PtdIns(4,5)P 2 was a candidate intracellular signal, and so it was discovered that Ins(l,4,5)/\ released Ca 2+ from endoplasmic reticulum (ER) (7). This intracellular release of Ca was found to be co-ordinated with an increase in the rate of Ca 2+ influx into the cell (7) -which finally confirmed the essence of the original idea (3) that inositol lipid turnover regulated Ca 2+ entry.Ins(l,4,5)P 3 -induced Ca 2+ release mediates an abundance of cellular responses as diverse as fertilization, cell growth and differentiation, neuronal signaling, secretion, and phototransduction. The distinct signaling requirements of individual cells are served by cell-and agonist-specific spatiotemporal patterns of Ca 2+ signaling. These arise not just from the binding of Ins(l,4,5)P 3 to its receptor, but also by modulation of this ligand/protein interaction by both cytosolic and ER-luminal Ca 2+ , and there is also input from the process of Ca 2+ entry, and Ins(l,4,5)P 3 metabolism (8). There is also regulatory diversity between the three major forms of the Ins(l,4,5)P 3 receptors that are currently recognized (see reference 9 for a review).

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Comparison of the levels of inositol metabolites in transformed haemopoietic cells and their normal counterparts

Cited by 86 publications

References 31 publications

Opposing Effects of Inositol Hexakisphosphate on Rod Arrestin and Arrestin2 Self-Association

Opposing Effects of Inositol Hexakisphosphate on Rod Arrestin and Arrestin2 Self-Association

Inositol hexakisphosphate in urine: the relationship between oral intake and urinary excretion

The Structural and Functional Versatility of Inositol Phosphates

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