Linked Life Data

7798217

Source:http://linkedlifedata.com/resource/pubmed/id/7798217

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
1995-1-24
pubmed:abstractText
The cAMP-dependent protein kinase (PKA) phosphorylates CREB327/341 at a single serine residue, Ser119/133, respectively. Phosphorylation at this site creates the sequence motif SXXXS(P), a consensus site of the glycogen synthase kinase-3 (GSK-3) enzyme (Fiol, C.J., Mahrenholz, A.M., Wang, Y., Roeske, R.W., and Roach, P.J. (1987) J. Biol. Chem. 262, 14042-14048). We examined the phosphorylation of CREB at the SXXXS(P) consensus site and its role in CREB transactivation to cAMP induction. Neither isoform of the GSK-3 enzyme (GSK-3 alpha or beta) utilizes CREB as its substrate unless CREB is already phosphorylated at Ser119/133. A 13-amino acid peptide containing the sequence surrounding Ser119/133 was phosphorylated by GSK-3, at Ser115/129, only after the primary phosphorylation of the peptide by PKA (at Ser119/133), suggesting that Ser115/129 is a GSK-3 phosphoacceptor site. Mutant CREB327/341 proteins containing Ser-->Ala substitutions confirmed Ser115/129 as the only GSK-3 phosphorylation site. Transfection assays of wild type and mutant Gal4-CREB fusion proteins in PC12 cells demonstrated that Ser-->Ala substitution of residue 129 of CREB341 impairs the transcriptional response to cAMP induction. Analogous mutation in CREB327 results in 70% decrease in its transactivation response to cAMP. In undifferentiated F9 cells, which are refractory to cAMP induction, transfected GSK-3 beta kinase induces a 60-fold increase in cyclic AMP response element-dependent transcription, mediated via the endogenous CREB protein. We propose that the hierarchical phosphorylation at the PKA and GSK-3 sites of CREB are essential for cAMP control of CREB.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32187-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7798217-Amino Acid Sequence, pubmed-meshheading:7798217-Animals, pubmed-meshheading:7798217-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:7798217-Cells, Cultured, pubmed-meshheading:7798217-Cyclic AMP, pubmed-meshheading:7798217-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:7798217-Gene Expression Regulation, pubmed-meshheading:7798217-Glycogen Synthase Kinase 3, pubmed-meshheading:7798217-Glycogen Synthase Kinases, pubmed-meshheading:7798217-Molecular Sequence Data, pubmed-meshheading:7798217-Mutation, pubmed-meshheading:7798217-PC12 Cells, pubmed-meshheading:7798217-Peptide Mapping, pubmed-meshheading:7798217-Phosphorylation, pubmed-meshheading:7798217-Plasmids, pubmed-meshheading:7798217-Rabbits, pubmed-meshheading:7798217-Rats, pubmed-meshheading:7798217-Serine, pubmed-meshheading:7798217-Transcriptional Activation, pubmed-meshheading:7798217-Transfection
pubmed:year
1994
pubmed:articleTitle
A secondary phosphorylation of CREB341 at Ser129 is required for the cAMP-mediated control of gene expression. A role for glycogen synthase kinase-3 in the control of gene expression.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't