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    Cell. 1989 Nov 17;59(4):675-80.

    Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.

    Gonzalez GA, Montminy MR.

    Source

    Clayton Foundation Laboratory for Peptide Biology, Salk Institute, La Jolla, California 92037.

    Abstract

    In this paper, we demonstrate that phosphorylation of CREB at Ser-133 is induced 6-fold in vivo, following treatment of PC12 cells with forskolin. By contrast, no such induction was observed in the kinase A-deficient PC12 line A126-1B2 (A126). Using F9 teratocarcinoma cells, which are unresponsive to cAMP, we initiated a series of transient expression experiments to establish a causal link between phosphorylation of CREB and trans-activation of cAMP-responsive genes. Inactivating the kinase A phosphorylation site by in vitro mutagenesis of the cloned CREB cDNA at Ser-133 completely abolished CREB transcriptional activity. As CREB mutants containing acidic residues in place of the Ser-133 phosphoacceptor were also transcriptionally inactive, these results suggest that phosphorylation of CREB may stimulate transcription by a mechanism other than by simply providing negative charge.

    PMID:
    2573431
    [PubMed - indexed for MEDLINE]

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