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Mol Cell Endocrinol. 2009 Jan 27;298(1-2):42-7. doi: 10.1016/j.mce.2008.10.023. Epub 2008 Oct 25.

PKA-dependent and independent cAMP signaling in 3T3-L1 fibroblasts differentiation.

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Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.


Adipogenesis is stimulated in 3T3-L1 fibroblast by a combination of insulin, dexamethasone, and methylisobutylxanthine (MIX). Mitotic clonal expansion (MCE) precedes differentiation of 3T3-L1 fibroblast to adipocytes. MIX increases cAMP content, which is the activator of protein kinase A (PKA). However, PKA-independent cAMP signaling has also been described. In this paper, it was found that H89, an inhibitor of PKA, was able to block MCE but not differentiation of 3T3-L1 fibroblast. Consistently, MCE did not occur in the absence of MIX in the differentiation mixture but was recovered by overexpression of a catalytic subunit of PKA. In addition, the transfection of 3T3-L1 fibroblast with a dominant-negative mutant of PKA inhibited MCE. On the other hand, differentiation of 3T3-L1 fibroblast to adipocytes did not occur when MIX was not present in the differentiation mixture and it could not be recovered by overexpression of a catalytic subunit of PKA. Differentiation was restored by addition of either dibutyryl-cAMP (db-cAMP) or 8 CPT-2 Me-cAMP. The latter activates cAMP-EPAC but not PKA signaling. These results indicate that cAMP-PKA-independent signaling, is required for 3T3-L1 fibroblasts differentiation to adipocytes and MIX signaling through cAMP-PKA is necessary for MCE, although MCE is not essential for adipogenesis.

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