Phosphorylation of conserved casein kinase sites regulates cAMP-response element-binding protein DNA binding in Drosophila

Horiuchi, J., Jiang, W., Zhou, H., Wu, P., Yin, J. C. (March 2004) Phosphorylation of conserved casein kinase sites regulates cAMP-response element-binding protein DNA binding in Drosophila. J Biol Chem, 279 (13). pp. 12117-25. ISSN 0021-9258 (Print)

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DOI: 10.1074/jbc.M212839200


The Drosophila homolog of cAMP-response element-binding protein (CREB), dCREB2, exists with serine 231, equivalent to mammalian serine 133, in a predominantly phosphorylated state. Thus, unlike the mammalian protein, the primary regulation of dCREB2 may occur at a different step from serine 231 phosphorylation. Although bacterially expressed dCREB2 bound cAMP-response element sites, protein from Drosophila extracts was unable to do so unless treated with phosphatase. Phosphorylation of recombinant protein by casein kinase (CK) I or II, but not calcium-calmodulin kinase II or protein kinase A, inhibited DNA binding. Up to four conserved CK sites likely to be phosphorylated in vivo were responsible for this effect, and these sites were phosphorylated by a kinase present in Drosophila cell extracts that biochemically resembles CKII. We propose that the relative importance of different signaling pathways in regulating CREB activity may differ between Drosophila and mammals. In Drosophila, the dephosphorylation of CK sites appears to be the major regulatory step, while phosphorylation of serine 231 is necessary but secondary.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Animals Genetically Modified Casein Kinases Cell Line Cyclic AMP metabolism Cyclic AMP Response Element-Binding Protein chemistry DNA chemistry Drosophila Drosophila melanogaster metabolism Electrophoresis Polyacrylamide Gel Molecular Sequence Data Mutagenesis Site-Directed Peptides chemistry Phosphorylation Plasmids metabolism Protein Binding Protein Kinases chemistry pharmacology Recombinant Proteins chemistry metabolism Sequence Homology Amino Acid Serine chemistry Transgenes
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
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Depositing User: CSHL Librarian
Date: 26 March 2004
Date Deposited: 03 Feb 2012 14:50
Last Modified: 03 Feb 2012 14:50

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