Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

Rasmus Koefoed Petersen; Lise Madsen; Lone Møller Pedersen; Philip Hallenborg; Hanne Hagland; Kristin Viste; Stein Ove Døskeland; Karsten Kristiansen

doi:10.1128/MCB.00709-07

Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

Rasmus Koefoed Petersen, Lise Madsen, Lone Møller Pedersen, Philip Hallenborg, Hanne Hagland, Kristin Viste, Stein Ove Døskeland, Karsten Kristiansen

104 Citations (Scopus)

Abstract

Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for cAMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of cAMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response.

Original language	English
Journal	Molecular and Cellular Biology
Volume	28
Issue number	11
Pages (from-to)	3804-3816
Number of pages	12
ISSN	0270-7306
DOIs	https://doi.org/10.1128/MCB.00709-07
Publication status	Published - 2008
Externally published	Yes

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Petersen, R. K., Madsen, L., Pedersen, L. M., Hallenborg, P., Hagland, H., Viste, K., Døskeland, S. O., & Kristiansen, K. (2008). Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes. Molecular and Cellular Biology, 28(11), 3804-3816. https://doi.org/10.1128/MCB.00709-07

Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes. / Petersen, Rasmus Koefoed; Madsen, Lise; Pedersen, Lone Møller et al.

In: Molecular and Cellular Biology, Vol. 28, No. 11, 2008, p. 3804-3816.

Research output: Contribution to journal › Journal article › Research › peer-review

Petersen, RK, Madsen, L, Pedersen, LM, Hallenborg, P, Hagland, H, Viste, K, Døskeland, SO & Kristiansen, K 2008, 'Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes', Molecular and Cellular Biology, vol. 28, no. 11, pp. 3804-3816. https://doi.org/10.1128/MCB.00709-07

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title = "Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes",

abstract = "Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for cAMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of cAMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response.",

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AU - Pedersen, Lone Møller

AU - Hallenborg, Philip

AU - Hagland, Hanne

AU - Viste, Kristin

AU - Døskeland, Stein Ove

AU - Kristiansen, Karsten

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AB - Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for cAMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of cAMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response.

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M3 - Journal article

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JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

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ER -

Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

Abstract

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