Proteomic analysis of cAMP-mediated signaling during differentiation of 3 T3-L1 preadipocytes

Kamil Borkowski, Krzysztow Wrzesinski, Adelina Rogowska-Wrzesinska, Karine Marie Laure Audouze, Jesse Bakke, Rasmus Koefoed Petersen, Fawaz G. Haj, Lise Madsen, Karsten Kristiansen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Initiation of adipocyte differentiation is promoted by the synergistic action of insulin/insulin-like growth factor, glucocorticoids, and agents activating cAMP-dependent signaling. The action of cAMP is mediated via PKA and Epac, where at least part of the PKA function relates to strong repression of Rho kinase activity, whereas Epac counteracts the reduction in insulin/insulin-like growth factor signaling associated with complete repression of Rho kinase activity. However, detailed knowledge of the Epac-dependent branch and the interplay with PKA is still limited. In the present study, we present a comprehensive evaluation of Epac-mediated processes and their interplay with PKA during the initiation of 3 T3-L1 preadipocyte differentiation using a combination of proteomics, molecular approaches, and bioinformatics. Proteomic analyses revealed 7 proteins specifically regulated in response to Epac activation, 4 in response to PKA activation, and 11 in response to the combined activation of Epac and PKA during the initial phase of differentiation. Network analyses indicated that the identified proteins are involved in pathways of importance for glucose metabolism, inositol metabolism, and calcium-dependent signaling thereby adding a novel facet to our understanding of cAMP-mediated potentiation of adipocyte differentiation.
    Original languageEnglish
    JournalB B A - Proteins and Proteomics
    Volume1844
    Issue number12
    Pages (from-to)2096-2107
    Number of pages12
    ISSN1570-9639
    DOIs
    Publication statusPublished - 2014

    Keywords

    • cAMP
    • Epac
    • Adipogenesis
    • Two-dimensional gel electrophoresis

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