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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.

Author information

1
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
DOI:
10.1016/0092-8674(89)90013-5
[Indexed for MEDLINE]

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