Effects of a sialoglycopeptide on early events associated with signal transduction

Toole-Simms, W.; Loder, D. K.; Fattaey, Heideh K.; Johnson, Terry C.

doi:10.1002/jcp.1041470214

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…31, consistent with earlier findings by Toole-Simms et al (1991). Thus, CeReS-18 does not inhibit cell proliferation by sequestering calcium directly and making the ion unavailable to the cell for cell cycle progression.…”

Section: Ceres-18supporting

confidence: 92%

“…4E and F). This decrease in the steady increase of intracellular calcium seen after the transient peak is probably due to 1986a; Toole-Simms et al, 1991;Betz et al, 1994). Evidence presented here further supports a role for calcium in the mechanism of action of CeReS-18 in mediating cell cycle arrest.…”

Section: Ceres-18supporting

confidence: 76%

“…Intracellular free calcium was determined based on the methods of Varani et al (1992) and Toole-Simms et al (1991). BALB/c 3T3 fibroblasts were cultured in 100 mm tissue culture dishes in complete medium until reaching approximately 50-70% confluency (in the presence or absence of CeReS-18, or 0.18 to 1.8 mM Ca").…”

Section: Measurement Of Intracellular Free Calciummentioning

confidence: 99%

“…Although the mechanism of action of the CeReS-18 which results in growth inhibition has not yet been elucidated, several lines of evidence suggest that calcium regulation may play an important role. Sharifi et al (1986a) showed that the inhibition of protein synthesis induced by CeReS-18 treatment could be blocked by exposure to the calcium ionophore A23187, and Toole-Simms et al (1991) demonstrated that CeReS-18 treatment inhibits the mobilization of intracellular calcium induced by TPA (12-0-tetradecanoyl phorbol-13acetate). In addition, recent studies in our laboratory have demonstrated the ability of extracellular calcium to influence the sensitivity of mouse keratinocytes to CeReS-18-induced growth inhibition (Betz et al, 1994).…”

mentioning

confidence: 99%

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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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Section: Ceres-18supporting

confidence: 92%

Section: Ceres-18supporting

confidence: 76%

Section: Measurement Of Intracellular Free Calciummentioning

confidence: 99%

mentioning

confidence: 99%

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

Betz

Westhoff

Johnson

1995

Journal Cellular Physiology

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“…CeReS-18 binds to a specific cell surface receptor (Sharifi and Johnson, 1987), and binding to this receptor correlates with DNA and protein synthesis inhibition (Bascom et al, 1986). Although the mechanism of action of the CeReS-18 growth inhibitor has not yet been elucidated, several lines of evidence suggest that calcium regulation and the retinoblastoma protein (Rb) may play important roles (Sharifi et al, 1986a;Toole-Simms et al, 1991;Johnson et al, 1992;Enebo et al, 1994).…”

mentioning

confidence: 99%

Calcium influences sensitivity to growth inhibition induced by a cell surface sialoglycopeptide

Betz

Fattaey

Johnson

1994

Journal Cellular Physiology

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While studies concerning mitogenic factors have been an important area of research for many years, much less is understood about the mechanisms of action of cell surface growth inhibitors. We have purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) which can reversibly inhibit the proliferation of diverse cell types. The studies discussed in this article show that three mouse keratinocyte cell lines exhibit sixty-fold greater sensitivity than other fibroblasts and epithelial-like cells to CeReS-18-induced growth inhibition. Growth inhibition induced by CeReS-18 treatment is a reversible process, and the three mouse keratinocyte cell lines exhibited either single or multiple cell cycle arrest points, although a predominantly G0/G1 cell cycle arrest point was exhibited in Swiss 3T3 fibroblasts. The sensitivity of the mouse keratinocyte cell lines to CeReS-18-induced growth inhibition was not affected by the degree of tumorigenic progression in the cell lines and was not due to differences in CeReS-18 binding affinity or number of cell surface receptors per cell. However, the sensitivity of both murine fibroblasts and keratinocytes could be altered by changing the extracellular calcium concentration, such that increased extracellular calcium concentrations resulted in decreased sensitivity to CeReS-18-induced proliferation inhibition. Thus the increased sensitivity of the murine keratinocyte cell lines to CeReS-18 could be ascribed to the low calcium concentration used in their propagation. Studies are currently under way investigating the role of calcium in CeReS-18-induced growth arrest. The CeReS-18 may serve as a very useful tool to study negative growth control and the signal transduction events associated with cell cycling.

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The identification of a naturally occurring cell surface growth inhibitor related to a previously described bovine sialoglycopeptide

Fattaey

Enebo

Moos

et al. 1993

J of Cellular Biochemistry

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A 66-kDa sialoglycoprotein has been identified as the parental membrane molecule of an earlier described sialoglycopeptide (SGP), an 18-kDa molecule released by protease treatment of intact bovine cerebral cortex cells that was shown to be a potent inhibitor of cellular proliferation. The 66-kDa parental sialoglycoprotein (p-SGP) was purified approximately 2,400-fold, to apparent homogeneity, from bovine cerebral cortex cell membranes by its release during incubation with 3 M NaCl, preparative isoelectric focusing and lectin affinity chromatography. Although a membrane-associated molecule, the p-SGP appeared to be tightly bound to the cell membrane, since it was not released during incubations in the absence of 3 M NaCl. Incubation of the membrane preparations with 3 M urea proved to be too harsh, and the antigenicity required to follow the purification of the p-SGP was abolished. Analyses by SDS-PAGE, under reducing and nonreducing conditions, suggested that the p-SGP membrane component was a single polypeptide without subunit structure. The p-SGP was shown to be structurally related to the SGP fragment by immunoblots with IgG raised to the SGP inhibitor, and functionally related to the SGP by its ability to inhibit Swiss 3T3 proliferation at concentrations strikingly similar to that previous measured with the SGP fragment.

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Effects of a sialoglycopeptide on early events associated with signal transduction

Cited by 8 publications

References 40 publications

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

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

Calcium influences sensitivity to growth inhibition induced by a cell surface sialoglycopeptide

The identification of a naturally occurring cell surface growth inhibitor related to a previously described bovine sialoglycopeptide

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