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. 1996 Feb;16(2):694–703. doi: 10.1128/mcb.16.2.694

Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism.

D Parker 1, K Ferreri 1, T Nakajima 1, V J LaMorte 1, R Evans 1, S C Koerber 1, C Hoeger 1, M R Montminy 1
PMCID: PMC231049  PMID: 8552098

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.

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Selected References

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