Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Molecular and Cellular Biology |
| Vol/bind | 28 |
| Udgave nummer | 11 |
| Sider (fra-til) | 3804-3816 |
| Antal sider | 12 |
| ISSN | 0270-7306 |
| DOI | |
| Status | Udgivet - 2008 |
| Udgivet eksternt | Ja |
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I: Molecular and Cellular Biology, Bind 28, Nr. 11, 2008, s. 3804-3816.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes
AU - Petersen, Rasmus Koefoed
AU - Madsen, Lise
AU - Pedersen, Lone Møller
AU - Hallenborg, Philip
AU - Hagland, Hanne
AU - Viste, Kristin
AU - Døskeland, Stein Ove
AU - Kristiansen, Karsten
PY - 2008
Y1 - 2008
N2 - 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.
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.
U2 - 10.1128/MCB.00709-07
DO - 10.1128/MCB.00709-07
M3 - Journal article
C2 - 18391018
SN - 0270-7306
VL - 28
SP - 3804
EP - 3816
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 11
ER -