The cyclic AMP-mediated stimulation of cell proliferation

Dumont, Jacques Emile; Jauniaux, Jean Claude; Roger, Pierre P.

doi:10.1016/0968-0004(89)90046-7

Cited by 442 publications

(240 citation statements)

References 28 publications

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“…The observation that tropic hormones activate cell proliferation and di erentiation through the cyclic AMP (cAMP)-dependent pathway suggested the possibility that G s proteins may be involved in the regulation of cell growth (Dumont et al, 1989). Identi®cation of the GTPase-inhibitory, activating GEFs, GDIs, GAPs (?…”

Section: G Proteins In the Regulation Of Cell Growth And DI Erentiationmentioning

confidence: 99%

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Regulation of cell proliferation by G proteins

Dhanasekaran

Tsim²,

Dermott³

et al. 1998

Oncogene

136

107

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G Proteins provide signal transduction mechanisms to seven transmembrane receptors. Recent studies have indicated that the a-subunits as well as the bg-subunits of these proteins regulate several critical signaling pathways involved in cell proliferation, di erentiation and apoptosis. Of the 17 a-subunits that have been cloned, at least ten of them have been shown to couple mitogenic signaling in ®broblast cells. Activating mutations in Ga s , Ga i2 , and Ga 12 have been correlated with di erent types of tumors. In addition, the ability of the bg-subunits to activate mitogenic pathways in di erent cell-types has been de®ned. The present review brie¯y summarizes the diverse and novel signaling pathways regulated by the a-as well as the bg-subunits of G proteins in regulating cell proliferation.

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Section: G Proteins In the Regulation Of Cell Growth And DI Erentiationmentioning

confidence: 99%

“…The signaling pathway mediated cAMP has been found to be mitogenic in hormone-dependent endocrine tissues such adrenal cortex, thyroid, ovary, pituitary, and testes (Dumont et al, 1989;Vallar, 1996). These cells are endowed with seven transmembrane receptors that are coupled to the adenylyl cyclase pathway through Ga s .…”

Section: Ga S and The Gsp Oncogenementioning

confidence: 99%

Regulation of cell proliferation by G proteins

Dhanasekaran

Tsim²,

Dermott³

et al. 1998

Oncogene

136

107

View full text Add to dashboard Cite

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“…Primary cultures of dog thyroid epithelial cells stimulated by thyrotropin (TSH) probably represent the best characterized example of positive control of DNA synthesis and G0-S prereplicative phase progression by cyclic (c)AMP [15,16]. In this physiologically relevant system [17,18], cAMP positively controls a late G1 R point [19].…”

Section: Introductionmentioning

confidence: 99%

Nature of the Critical Labile Event That Controls RB Phosphorylation in the Cyclic AMP-Dependent Cell Cycle of Thyrocytes in Primary Culture

Roger

Demartin

Dumont

1999

Experimental Cell Research

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This study addresses the nature of the critical labile event that couples at restriction point mitogenic cascades with the autonomous part of the cell cycle. In primary cultures of dog thyroid epithelial cells, kinetic experiments indicate that a labile cAMP-dependent event positively controls a late G1 commitment to DNA replication and RB phosphorylation. As previously shown in this system, the cAMP-dependent mitogenic pathway differs from the most generally envisaged growth factor cascades as it stimulates the accumulation of p27 kip1 but not of cyclins D. Nevertheless, cyclin D3 and CDK4 activity are essential in the cAMP-dependent mitogenesis, and cAMP unmasks the DCS-22 epitope of cyclin D3 and induces the nuclear translocations and assembly of cyclin D3 and CDK4 in a complex that also contains p27 kip1 . Unexpectedly, the washing out of forskolin rapidly arrested S phase entry and the accumulation of hyperphosphorylated RB, but did not reverse any of the above events associated with cyclin D3-CDK4 activation. This implies that even after induction of stable nuclear cyclin D3-CDK4 complexes, dog thyrocytes still depend on cAMP for RB phosphorylation and commitment to DNA synthesis, which suggests that a key labile event responsible for a last control of restriction point passage remains to be uncovered, in the cAMP-dependent cell cycle of dog thyrocytes and possibly other systems.

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“…The mechanisms whereby signalling pathways direct apoptosis appear to be complex and cell type-speci®c. Indeed, cAMP induces apoptosis in thymocytes McConkey et al, 1992;Susuki et al, 1990), while it stimulates proliferation of epithelial cells and neuronal cell di erentiation (Freidman, 1976;Dumont et al, 1989). Importantly, cAMP synergises with glucocorticoids and PKC signalling in inducing apoptosis (McConkey et al, 1990;Susuki et al, 1990;Groul and Altschmeid, 1993;reviewed in McConkey et al, 1992), while it cooperates with retinoids in the di erentiation of teratocarcinoma cells (Hu and Gudas, 1990;WeilerGuetter et al, 1992) and of various leukaemia cells (Olsson et al, 1982;Gianni et al, 1995;Ruchaud et al, 1994).…”

Section: Introductionmentioning

confidence: 99%