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

Cell | Nov 17, 1989

http://www.ncbi.nlm.nih.gov/pubmed/2573431

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.

Pubmed ID: 2573431 RIS Download

Mesh terms: Adrenal Gland Neoplasms | Amino Acid Sequence | Animals | Base Sequence | Cell Line | Colforsin | Cyclic AMP | Cyclic AMP Response Element-Binding Protein | DNA-Binding Proteins | Genes | Molecular Sequence Data | Mutation | Peptide Mapping | Pheochromocytoma | Phosphorylation | Rats | Serine | Somatostatin | Transcription, Genetic | Transfection