Regulation of protein kinase and phosphoprotein phosphatase by cyclic AMP and cyclic AMP antagonist

Wasner, H.K.; Sutherland, Earl W.

doi:10.1016/0014-5793(75)80152-9

Cited by 26 publications

(21 citation statements)

References 10 publications

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“…The name cAMP antagonist used here for this new, intracellular, hormone messenger-like regulator merely denotes the fact that this substance acts in an antagonistic fashion to cAMP by inhibiting cAMP-dependent protein kinases and activating phosphoprotein phosphatases [5]. After stimulation of hepatocytes with insulin a substance can be isolated [7] with properties so far indistinguishable from that in adrenalin-stimulated hepatocytes, in that it behaves identically during chromatographic purification, and it inhibits pro-…”

Section: Discussionmentioning

confidence: 99%

“…cAMP antagonist activity was assayed b3): (i) Inhibition of cAMP-dependent protein kinase as in [5]; (ii) Its ability to inhibit adenylate cyclase. Fractions of 10-50 gl containing cAMP antagonist were added to 600 gl of the adenylate cyclase assay mixture, when purified plasma membranes were used [9].…”

Section: Assay Of Camp An Tagonistmentioning

confidence: 99%

“…In [11] prostaglandin E (PGE) inhibited adenylate tein kinase, activates phosphoprotein phosphatase [ 5,7 ] and activates pyruvate dehydrogenase [ 13]. These findings suggest that cAMP antagonist is an intracellular mediator of the action of a set of different (perhaps anabolic) hormones just as cAMP mediates the action of a number of different hormones.…”

Section: Role Of Prostaglandin E In Camp Antagonist Synthesismentioning

confidence: 99%

“…In [5,6] the regulatory properties of a second messenger-type regulator were described, which inhibits adenylate cyclase and protein kinase and activates phosphoprotein phosphatase. Because of this counteraction to cAMP it was named cAMP antagonist, cAMP antagonist appears to be a mediator [7] of hormonally controUed switch-off mechanism in liver, muscle, heart and brain, since it inhibits the cAMP-dependent protein kinases in these tissues [5].…”

Section: Introductionmentioning

confidence: 99%

“…Because of this counteraction to cAMP it was named cAMP antagonist, cAMP antagonist appears to be a mediator [7] of hormonally controUed switch-off mechanism in liver, muscle, heart and brain, since it inhibits the cAMP-dependent protein kinases in these tissues [5]. This report describes the biosynthesis and purification of cAMP antagonist.…”

Section: Introductionmentioning

confidence: 99%

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Biosynthesis of cyclic AMP antagonist in hepatocytes from rats after adrenalin‐ or insulin‐stimulation

Wasner

1981

FEBS Letters

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Section: Discussionmentioning

confidence: 99%

Section: Assay Of Camp An Tagonistmentioning

confidence: 99%

Section: Role Of Prostaglandin E In Camp Antagonist Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biosynthesis of cyclic AMP antagonist in hepatocytes from rats after adrenalin‐ or insulin‐stimulation

Wasner

1981

FEBS Letters

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Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger of insulin action. Comparative analysis of two kinds of ‘insulin mediators’

Shashkin

Wasner

Ortmeyer

et al. 2001

Diabetes Metabolism Res

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Insulin induces a broad spectrum of effects over a wide time interval. It also stimulates the phosphorylation of some cellular proteins, while decreasing the state of phosphorylation of others. These observations indicate the presence of different, but not necessarily mutually exclusive, pathways of insulin action. One well-known pathway represents a phosphorylation cascade initiated by the tyrosine kinase activity of the insulin receptor followed by involvement of different MAP-kinases. Another pathway suggests the existence of low molecular weight insulin mediators whose synthesis and/or release is initiated by insulin. Comparable analysis of two kinds of insulin mediators, namely inositolphosphoglycans and prostaglandylinositol cyclic phosphate (cPIP), has been carried out. It has been shown that the expression of a number of enzymes, such as phospholipase A(2), phospholipase C, cyclo-oxygenase and IRS-1-like enzyme, could regulate the biosynthesis of cPIP in both normal and diabetes-related conditions. Data on the activity of a key enzyme of cPIP biosynthesis termed cPIP synthase (IRS-1-like enzyme) in various monkey tissues before and twice during an euglycemic hyperinsulinemic clamp have been presented. It has been concluded that in vivo insulin increases cPIP synthase activity in both liver and subcutaneous adipose tissue of lean normal monkeys. It has been also suggested that abnormal production of cPIP could be related to several pathologies including glucocorticoid-induced insulin resistance and diabetic embryopathy. Further studies on cPIP and other types of insulin mediators are necessary to aid our understanding of insulin action.

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Prostaglandylinositol cyclic phosphate, the natural antagonist of cyclic AMP

Wasner

2020

IUBMB Life

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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.

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Regulation of protein kinase and phosphoprotein phosphatase by cyclic AMP and cyclic AMP antagonist

Cited by 26 publications

References 10 publications

Biosynthesis of cyclic AMP antagonist in hepatocytes from rats after adrenalin‐ or insulin‐stimulation

Biosynthesis of cyclic AMP antagonist in hepatocytes from rats after adrenalin‐ or insulin‐stimulation

Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger of insulin action. Comparative analysis of two kinds of ‘insulin mediators’

Prostaglandylinositol cyclic phosphate, the natural antagonist of cyclic AMP

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