Degradation of the Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) by Dephosphorylation

Kassner, Astrid; Lessmann, M.; Wasner, H.K.

doi:10.1515/bc.1999.011

Cited by 5 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors conclude that inactivation of the enzyme is connected with protein tyrosine defosforylation. The cPIP degrading activities have been found in all rat tissues tested, but are highest in the liver and lowest in the brain [116]. Inhibition of PG synthesis by the drug indomethacin suppresses the synthesis of cPIP in rat liver and leads to a metabolic state comparable to diabetes type 2 [117].…”

Section: N O T F O R D I S T R I B U T I O Nmentioning

confidence: 97%

Fluoride Interactions: From Molecules to Disease

Strunecká¹,

Patočka²,

Blaylock³

et al. 2007

CST

View full text Add to dashboard Cite

Fluoride has long been known to influence the activity of various enzymes in vitro. Later it has been demonstrated that many effects primarily attributed to fluoride are caused by synergistic action of fluoride plus aluminum. Aluminofluoride complexes have been widely used as analogues of phosphate groups to study phosphoryl transfer reactions and heterotrimeric G proteins involvement. A number of reports on their use have appeared, with far-reaching consequences for our understanding of fundamental biological processes. Fluoride plus aluminum send false messages, which are amplified by processes of signal transduction. Many investigations of the longterm administration of fluoride to laboratory animals have demonstrated that fluoride and aluminofluoride complexes can elicit impairment of homeostasis, growth, development, cognition, and behavior. Ameliorative effects of calcium, vitamins C, D, and E have been reported. Numerous epidemiological, ecological, and clinical studies have shown the effects of fluoride on humans. Millions of people live in endemic fluorosis areas. A review of fluoride interactions from molecules to disease is necessary for a sound scientific assessment of health risks, which may be linked to the chronic intake of small doses of fluoride and aluminum from environmental and artificial sources.

show abstract

Section: N O T F O R D I S T R I B U T I O Nmentioning

confidence: 97%

Fluoride Interactions: From Molecules to Disease

Strunecká¹,

Patočka²,

Blaylock³

et al. 2007

CST

View full text Add to dashboard Cite

show abstract

“…It is a prostaglandylinositol cyclic phosphate, which activates serine/threonine protein phosphatases and inhibits protein kinases A (Wasner, 1975). It appears to be ubiquitous like cyclic AMP and can be isolated from various rat organs, from yeast (Wasner and Salge, 1987) or the slime mould Dictyostelium discoideum (Kaiser et al, 1998). It is synthesized by the plasma membrane-bound enzyme cyclic PIP synthase by combining prostaglandin E (PGE) and activated inositol phosphate (n-IP), which appears to be a guanosine diphosphoinositol cyclic phosphate (Gypakis and Wasner, 1996).…”

Section: Introductionmentioning

confidence: 99%

Two Different Mechanisms for Activation of Cyclic PIP Synthase: by a G Protein or by Protein Tyrosine Phosphorylation

Wasner¹,

Gebel²,

Hucken³

et al. 2000

Biological Chemistry

View full text Add to dashboard Cite

The biosynthesis of the functional, endogenous cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP) is performed by the plasma membrane-bound enzyme cyclic PIP synthase, which combines prostaglandin E (PGE) and activated inositol phosphate (n-IP) to cyclic PIP. The Km values of the enzyme for the substrates PGE and n-IP are in the micromolar range. The plasma membrane-bound synthase is activated by fluoride, by the stable GTP analog GMP-PNP, by protamine or biguanide, by noradrenaline, and by insulin. The activation by protamine or biguanide and fluoride (10 mM) is additive, which may indicate the presence of two different types of enzyme, comparable to phospholipase Cbeta and phospholipase Cgamma. Plasma membrane-bound cyclic PIP synthase is inhibited by the protein tyrosine kinase inhibitor tyrphostin B46 with an IC50 of 1.7 microM. However, the solubilized and gel-filtrated enzyme is no longer inhibited by tyrphostin, indicating that the activity of cyclic PIP synthase is connected with the activity of a membrane-bound protein tyrosine kinase. Cyclic PIP synthase activity of freshly prepared plasma membranes is unstable. Upon freezing and rethawing of liver plasma membranes, this instability is increased about 2-fold. Protein tyrosine phosphatase inhibitors [vanadate, fluoride (50-100 mM)] stabilize the enzyme activity, but protease inhibitors do not, indicating that inactivation of the enzyme is connected with protein tyrosine dephosphorylation. Cyclic PIP synthase is present in all tissues tested, like brain, heart, intestine, kidney, liver, lung, skeletal muscle, spleen, and testis. Apart from liver, cyclic PIP synthase activity in most tissues is rather low, but it can be increased up to 5-fold when protein tyrosine phosphatase inhibitors like vanadate are present in the homogenization buffer. Preincubation of cyclic PIP synthase of liver plasma membranes with the tyrosine kinase src kinase causes a 2-fold increase of cyclic PIP synthase activity, though this is certainly not the physiological role played by src kinase in intact cells. The data indicate that cyclic PIP synthase can be activated by two separate mechanisms: by a G protein or by protein tyrosine phosphorylation.

show abstract

“…So far, no drug has been found, which inhibits the degradations of cyclic PIP. 30 For this reason, only small amounts of cyclic PIP can be isolated. 8 In part, cyclic PIP is degraded by β-oxidation of the PGEmoiety, which leads to the dinor-PGE 1 analog of cyclic PIP.…”

Section: Chemical Structure Biosynthesis and Degradation Of Cyclimentioning

confidence: 99%

“…Cyclic PIP synthesis was characterized in livers of rhesus monkeys 12 . and in Dictyostelium discoideum 13 . The synthesis of cyclic PIP increases with increasing concentration of hormones that stimulate its synthesis 8 …”

Section: There Is a Counterpart To Cyclic Ampmentioning

confidence: 99%

Prostaglandylinositol cyclic phosphate, the natural antagonist of cyclic AMP

Wasner

2020

IUBMB Life

View full text Add to dashboard Cite

While searching for a counterpart to cyclic AMP, a new compound was found to inhibit adenylate cyclase. It was identified as prostaglandyl-(15-4 0)-myo-inositol (1 0 :2 0-cyclic)-phosphate (cyclic PIP). The substrates for its biosynthesis are prostaglandin E (PGE) and the novel inositol phosphate, guanosine diphospho-4-myoinositol 1:2-cyclic phosphate (n-IP). The basic regulatory properties of cyclic PIP are to inhibit dose-dependently protein kinase A (PKA) and to seven-fold activate protein ser/thr phosphatase holoenzyme. These regulations occur as rapidly as the activation of PKA by cyclic AMP. Such regulatory properties are essential for the meticulous regulation of the equilibrium between the phospho-and de-phospho-form of interconvertible enzymes. The synthesis of cyclic PIP is stimulated by insulin and noradrenaline (α-receptor action). The insulin-stimulated cyclic PIP synthase is active in a tyrosine-phosphorylated state. A comparable characterization of the adrenaline-stimulated cyclic PIP synthase is still incomplete. In streptozotocin-diabetic rats, the hormonal stimulation of cyclic PIP synthesis decreases with time. Cyclic PIP synthesis is activated by biguanides as metformin two to four-fold and by antihypertensive drugs twofold. Inhibition of cyclic PIP synthesis leads to a metabolic state as observed in early-stage type-2 diabetes. In summary, all living cells synthesize cyclic PIP, which switches on anabolism, whereas cyclic AMP triggers catabolism.

show abstract

Degradation of the Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) by Dephosphorylation

Cited by 5 publications

References 12 publications

Fluoride Interactions: From Molecules to Disease

Fluoride Interactions: From Molecules to Disease

Two Different Mechanisms for Activation of Cyclic PIP Synthase: by a G Protein or by Protein Tyrosine Phosphorylation

Prostaglandylinositol cyclic phosphate, the natural antagonist of cyclic AMP

Contact Info

Product

Resources

About