Induction of growth in resting fibroblastic cell cultures by Ca++.

Dulbecco, Renato; Elkington, Jane

doi:10.1073/pnas.72.4.1584

Cited by 139 publications

(52 citation statements)

References 17 publications

(13 reference statements)

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“…The effect of increased calcium concentrations in the medium on 3H-TdR incorporation substantially confirm the findings of Dulbecco and Elkington (1). Simialar experiments have been carried out with the addition of other divalent cations (zinc, nickel, magnesium, manganese) to the medium but no stimulation of thymidine incorporation similar to that observed in the presence of additional calcium were found (Damluji and Riley, unpubl.…”

Section: Discussionsupporting

confidence: 74%

“…Several authors (1)(2)(3) have reported that the serum-induced proliferation of quiescent 3T3 cells is characterised by alterations in the amount of calcium associated with the cells suggesting that serum stimulation of growth may be mediated in part through changes in the concentrations or localization of calcium. In this communication we demonstrate a phase in the initiation of cell proliferation during which the cells are sensitive to external calcium levels which implies that cell-associated calcium acts as a cofactor in the effect of serum.…”

Section: Introductionmentioning

confidence: 99%

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Time Dependency of a Critical Effect of EGTA on DNA Synthesis in Cultures of Swiss 3T3 Cells

Damluji¹,

Riley²

1979

Pathobiology

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In a temporal analysis of the mitogenic response to serum, a critical period has been demonstrated just prior to the onset of replicative DNA synthesis during which transient calcium depletion blocks the subsequent entry of the cells into the S phase of the mitotic cycle. Transient washing of monolayer cultures of 3T3 cells with 2.5 mM EGTA between 6 and 8 h after serum-stimulated initiation of DNA synthesis was found to reduce cell-associated calcium levels and to inhibit thymidine incorporation, whereas similar treatment before (1–5 h) and after (8–9 h) had no detectable effect on either of these parameters when estimated after 21 h incubation. The effects during the chelation-sensitive period were reversed by the subsequent addition of fresh serum.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Time Dependency of a Critical Effect of EGTA on DNA Synthesis in Cultures of Swiss 3T3 Cells

Damluji¹,

Riley²

1979

Pathobiology

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“…Since extracellular calcium affects cell growth (Dulbecco and Elkington, 1975;Hazelton et al, 1979;Paul and Ristow, 1979;Nicholson et al, 1984;Kulesz-Mar-…”

Section: Calcium Does Not Alter Ceres-18 Binding Characteristics and mentioning

confidence: 99%

Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

Betz

Westhoff

Johnson

1995

Journal Cellular Physiology

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Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB-c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS-18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS-18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18-induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10-fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression.

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“…Since growth is usually required for division, the cells of many organisms, including prokaryotic (4) and eukaryotic (5-9) microorganisms, metazoa (10)(11)(12)(13)(14)(15)(16)(17), and metaphyta (18), control division in response to inorganic and organic nutrients. Some evidence exists to suggest that even the protein growth factors of mammalian cells such as serum factors and agglutinins may act by enhancing the availability of small molecular weight nutrients (19,20).…”

mentioning

confidence: 99%

Control of cell division in Saccharomyces cerevisiae by methionyl-tRNA.

Unger¹,

Hartwell²

1976

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

135

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We suggest that two events are necessary for an asynchronous population of cells to undergo arrest in the GI phase of the cell cycle upon nutrient starvation. First, passage through GI must be prevented by a deficiency of some metabolic intermediate. Since this intermediate may act indirectly to arrest division, we designate it the "signal." We have found three conditions under which Saccharomyces cerevisiae cells arrest division in GI: sulfate starvation of a prototroph, methionine starvation of an auxotroph, or a shift of a conditional methionyl-tRNA synthetase mutant [ILmethionine:tRNAMet ligase (AMP-forming), EC 6.1.1.10 Ito a restrictive condition. We interpret these results to indicate that the signal for sulfate starvation in S. cerevisiae is generated near the end of the sulfate assimilation pathway (at or beyond the formation of methionyl-tRNA). As a unifying hypothesis, we propose that the signal for all nutrients is generated at the level of protein biosynthesis.A second event necessary for GI arrest is the provision of sufficient protein synthetic capacity for cells to finish the cycles that are in progress when the signal is generated. This necessity is demonstrated by the failure of the methionyl-tRNA synthetase mutant to undergo GI arrest when protein synthesis is abruptly terminated by a shift to 36°into methionine-deficient medium.Many eukaryotic cells pass reversibly from a proliferative to a non-proliferative state and, in most cases that have been studied, division is arrested in the G1 interval of the cell cycle (1-3). Since growth is usually required for division, the cells of many organisms, including prokaryotic (4) and eukaryotic (5-9) microorganisms, metazoa (10-17), and metaphyta (18), control division in response to inorganic and organic nutrients. Some evidence exists to suggest that even the protein growth factors of mammalian cells such as serum factors and agglutinins may act by enhancing the availability of small molecular weight nutrients (19,20 (mesl-). Strains with the prefix DU were constructed by first mating a haploids to the a-haploid EMS-63 and then producing homozygosity of the mutation for methionine auxotrophy by x-ray-induced mitotic recombination (25). The haploid EMS-63 was supplied by Dr. Gerald Fink (Cornell University).The pathway of methionine biosynthesis has been discussed by Masselot and Robichon-Szulmajster (26). The methionine auxotrophs used in this paper are representative of the possible levels in the methionine biosynthetic pathway. Only three gene-enzyme assignments have been documented; the met2-mutant is defective in homoserine-O-transacetylase, met25-is defective in homocysteine synthetase, and mesa is defective in methionyl-tRNA synthetase [L-methionine:tRNAMet ligase (AMP-forming), EC 6.1. 1.101 (26, 27). Strains carrying the mes mutation exhibit two phenotypes, a methionine auxotrophy and a temperature-sensitivity. We have undertaken a genetic and biochemical study of this mutation. The results show that both phenotypes are due to a sing...

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Induction of growth in resting fibroblastic cell cultures by Ca++.

Cited by 139 publications

References 17 publications

Time Dependency of a Critical Effect of EGTA on DNA Synthesis in Cultures of Swiss 3T3 Cells

Time Dependency of a Critical Effect of EGTA on DNA Synthesis in Cultures of Swiss 3T3 Cells

Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

Control of cell division in Saccharomyces cerevisiae by methionyl-tRNA.

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