IMR Press / FBE / Volume 2 / Issue 2 / DOI: 10.2741/E99

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Epac, not PKA catalytic subunit, is required for 3T3-L1 preadipocyte differentiation
Show Less
1 Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Brach, Galveston, Texas 77555-0616, USA

*Author to whom correspondence should be addressed.

Academic Editor: Silvio Naviglio

Front. Biosci. (Elite Ed) 2010, 2(2), 392–398; https://doi.org/10.2741/E99
Published: 1 January 2010
(This article belongs to the Special Issue Adenylate cyclasecAMP axis and cell growth)
Abstract

Cyclic AMP plays a critical role in adipocyte differentiation and maturation. However, it is not clear which of the two intracellular cAMP receptors, exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor or protein kinase A/cAMP-dependent protein kinase, is essential for cAMP-mediated adipocyte differentiation. In this study, we utilized a well-defined adipose differentiation model system, the murine preadipocyte line 3T3-L1, to address this issue. We showed that knocking down Epac expression in 3T3-L1 cells using lentiviral based small hairpin RNAs down-regulated peroxisome proliferator-activated receptor gamma expression and dramatically inhibited adipogenic conversion of 3T3-L1 cells while inhibiting PKA catalytic subunit activity by two mechanistically distinct inhibitors, heat stable protein kinase inhibitor and H89, had no effect on 3T3-L1 adipocyte differentiation. Moreover, cAMP analog selectively activating Epac was not able to stimulate adipogenic conversion. Our study demonstrated that while PKA catalytic activity is dispensable, activation of Epac is necessary but not sufficient for adipogenic conversion of 3T3-L1 cells.

Keywords
Cyclic AMP
Epac
Exchange protein directly activated by cAMP
PKA (Protein kinase A)
PPARγ
Peroxisome proliferator-activated receptor γ
3T3-L1
Adipogenesis
Adipocyte
Differentiation
Share
Back to top