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PKA-dependent and independent cAMP signaling in 3T3-L1 fibroblasts differentiation
Ist Teil von
Molecular and cellular endocrinology, 2009-01, Vol.298 (1), p.42-47
Ort / Verlag
Ireland: Elsevier Ireland Ltd
Erscheinungsjahr
2009
Link zum Volltext
Quelle
Elsevier ScienceDirect Journals Complete
Beschreibungen/Notizen
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.