Cyclic AMP in Metobolism

Pastan, Ira; Perlman, Robert L.

doi:10.1038/newbio229005a0

Cited by 83 publications

(27 citation statements)

References 52 publications

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“…Even though we have introduced an arbitrary distinction between the effects of cAMP on specific differentiated functions (30) and on the more general pleiotypic parameters of growth, we do not wish to imply that the molecular mechanisms of cAMP action need be different in the two cases. It is generally agreed that protein kinase activation is the basis for the cAMP-mediated effects on specific cellular functions, such as the glycogenolysis.…”

Section: Discussionmentioning

confidence: 99%

Pleiotypic Control by Adenosine 3′:5′-Cyclic Monophosphate: A Model for Growth Control in Animal Cells

Kram

Mamont

Tomkins

1973

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

145

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The effects of serum deprivation on several general cellular biochemical processes ("pleiotypic response") related to the growth of normal fibroblasts can be mimicked by treatment of these cells with prostaglandin El in the presence of serum. N8,02'-Dibutyryl adenosine 3': 5'-cyclic monophosphate and theophylline inhibit the membrane transport processes without much effect on other pleiotypic reactions such as overall protein and RNA synthesis and protein degradation. The amount of intracellular cyclic AMP increases during serum starvation and returns to the initial concentration in unstarved cells when growth is initiated again upon addition of serum. Fibroblasts transformed by simian virus 40 have a lower cyclic AMP content than their untransformed parents. Serum deprivation neither increases cyclic AMP content nor significantly affects the pleiotypic reactions in transformed cells. Cycloheximide causes a decrease in cyclic AMP content of normal fibroblasts coincidentally with the ability of this inhibitor to stimulate uridine transport and slow protein degradation in cells deprived of serum.In normal cells, several biochemical parameters, including membrane transport, overall rates of protein and RNA synthesis, and protein degradation, fluctuate coordinately with changes in cell-growth rate. These mechanistically unrelated processes and their coordinated response to environmental changes comprise what we have defined as the "pleiotypic program" and "pleiotypic control," respectively. In malignant cells, the pleiotypic program and the rate of growth are relatively insensitive to changes in cultural conditions; we thus picture transformed cells as having a defect in the pleiotypic control mechanism (1).In cultured fibroblasts, insulin as well as serum activates the pleiotypic program (1, 2). Moreover, the same set of reactions is regulated in many other cell types by specific hormones or growth factors. Thus, certain general features of hormonal regulation may also be exerted through the pleiotypic mechanism (1).We have postulated that a "mediator", probably formed at the cell membrane, coordinates the responses of the different reactions under pleiotypic control. Because of the resemblance of this regulatory program to "stringent control" in bacteria, we inquired whether guanosine 5'-diphosphate, 2'-or 3'-diphosphate (ppGpp) (a possible mediator of stringent control) (3, 4) could be involved in control in animal cells. However, this nucleotide was not detected in cultured 3T3 cells under conditions that should have elicited its appearance (5).In the meantime, numerous reports have implicated cAMP as a regulator of growth, morphology, and contact inhibition in cultured cells (6-11). We report here that altering the inAbbreviations: Bu2cAMP, N6,02'-dibutyryl adenosine 3':5'-cyclic monophosphate; PGE,, prostaglandin El; SV40, simian virus 40. tracellular cAMP content by various means can affect all the reactions under pleiotypic control in a way, suggesting that cAMP is very likely the pleiotypic mediator...

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Section: Discussionmentioning

confidence: 99%

Pleiotypic Control by Adenosine 3′:5′-Cyclic Monophosphate: A Model for Growth Control in Animal Cells

Kram

Mamont

Tomkins

1973

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

145

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“…In animal cells, cyclic AMP is involved in the control of several metabolic pathways, through the regulation of the activity of many enzymes [4]. Presumably, as in the case of bacterial cells, some actions of cyclic AMP are mediated by changes in the rate of synthesis of RNA.…”

Section: Introductionmentioning

confidence: 99%

Stimulation by cyclic 3′,5′‐adenosine monophosphate of RNA synthesis in a mammalian cell‐free system

1972

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“…This phenomenon, originally termed the 'glucose effect' (Monod, 1942), is made up of at least two components (Lengeler, 1966 Monod, 1968;Pastan & Perlman, 1970, 1971 …”

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confidence: 99%

“…By 'catabolite inhibition' (McGinnis & Paigen, 1969), glucose inhibits the uptake of other carbohydrates; by 'catabolite repression' (Magasanik, 1961), glucose (or some product of glucose metabolism) represses the synthesis ofenzymes that would normally be induced by those other carbohydrates. It has been established that, for a number of inducible enzymes, the repressive effect of glucose is associated with a lowering of the intracellular concentrations of adenosine 3': 5'-cyclic monophosphate (cyclic AMP), and that the addition of cyclic AMP to the bacterial cultures permits induction of these enzymes to occur even in the presence of glucose (Ullman & Monod, 1968;Pastan & Perlman, 1970, 1971. However, it has sidase even greater than does glucose (Okinaka & Dobrogosz, 1967), and that the repression produced by a combination ofgluconate and glucose is so severe that external cyclic AMP is not able to reverse it (Goldenbaum & Dobrogosz, 1968 (Brice & Kornberg, 1967) was used as a'wild-type' strain.…”

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confidence: 99%

Utilization of gluconate by Escherichia coli. A role of adenosine 3′:5′-cyclic monophosphate in the induction of gluconate catabolism

Bächi¹,

Kornberg²

1975

Biochemical Journal

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1. Cultures of Escherichia coli growing on gluconate use both gluconate and glucose when glucose is added. 2. Glycerol-grown cells adapt to gluconate utilization even in media containing glucose as well as gluconate. 3. The rates of gluconate utilization by cells growing on a mixture ofglucose and gluconate, and the specific activities ofthe gluconate uptake system and of gluconate kinase, are greater if adenosine 3': 5'-cyclic monophosphate (cyclic AMP) is present in the medium than in its absence. 4. Growth on media containing gluconate and cyclic AMP is accompanied by the formation of methyl glyoxal and pyruvate, and progressive inhibition of growth. 5. A mutant devoid of adenylate cyclase activity (cya) grew well on glucose in the absence of exogenous cyclic AMP but grew only poorly on gluconate; neither the gluconate uptake system nor gluconate kinase was adequately induced. The addition of cyclic AMP promoted growth on gluconate and facilitated the induction of proteins required for gluconate catabolism. 6. Phage P1-mediated transduction of cya+ into the cya-mutant also restored the wild-type phenotype in its ability to adapt to gluconate utilization.When cultures of Escherichia coli are placed in growth media containing both glucose and any one of a wide range of carbohydrates, glucose is used preferentially and the proteins required for the uptake and catabolism of the other carbohydrate are inducibly formed only after the glucose has been virtually used up. This phenomenon, originally termed the 'glucose effect' (Monod, 1942), is made up of at least two components (Lengeler, 1966 Monod, 1968;Pastan & Perlman, 1970, 1971

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Cyclic AMP in Metobolism

Cited by 83 publications

References 52 publications

Pleiotypic Control by Adenosine 3′:5′-Cyclic Monophosphate: A Model for Growth Control in Animal Cells

Pleiotypic Control by Adenosine 3′:5′-Cyclic Monophosphate: A Model for Growth Control in Animal Cells

Stimulation by cyclic 3′,5′‐adenosine monophosphate of RNA synthesis in a mammalian cell‐free system

Utilization of gluconate by Escherichia coli. A role of adenosine 3′:5′-cyclic monophosphate in the induction of gluconate catabolism

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