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PMID:8552098

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Citation

Parker, D, Ferreri, K, Nakajima, T, LaMorte, VJ, Evans, R, Koerber, SC, Hoeger, C and Montminy, MR (1996) Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism. Mol. Cell. Biol. 16:694-703

Abstract

We have characterized a phosphoserine binding domain in the coactivator CREB-binding protein (CBP) which interacts with the protein kinase A-phosphorylated, and hence activated, form of the cyclic AMP-responsive factor CREB. The CREB binding domain, referred to as KIX, is alpha helical and binds to an unstructured kinase-inducible domain in CREB following phosphorylation of CREB at Ser-133. Phospho-Ser-133 forms direct contacts with residues in KIX, and these contacts are further stabilized by hydrophobic residues in the kinase-inducible domain which flank phospho-Ser-133. Like the src homology 2 (SH2) domains which bind phosphotyrosine-containing peptides, phosphoserine 133 appears to coordinate with a single arginine residue (Arg-600) in KIX which is conserved in the CBP-related protein P300. Since mutagenesis of Arg-600 to Gln severely reduces CREB-CBP complex formation, our results demonstrate that, as in the case of tyrosine kinase pathways, signal transduction through serine/threonine kinase pathways may also require protein interaction motifs which are capable of recognizing phosphorylated amino acids.

Links

PubMed PMC231049

Keywords

3T3 Cells; Amino Acid Sequence; Animals; Binding Sites; Binding, Competitive; CREB-Binding Protein; Circular Dichroism; Cross-Linking Reagents; Cyclic AMP/pharmacology; Cyclic AMP Response Element-Binding Protein/metabolism; Cyclic AMP-Dependent Protein Kinases/metabolism; Mice; Models, Biological; Molecular Sequence Data; Mutagenesis; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Peptide Fragments/genetics; Peptide Fragments/metabolism; Phosphorylation; Promoter Regions, Genetic; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Serine/metabolism; Trans-Activators; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CREB1

enables

GO:0003712: transcription coregulator activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete


See also

References

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