Linked Life Data

7958915

Source:http://linkedlifedata.com/resource/pubmed/id/7958915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1994-12-15
pubmed:abstractText
The cAMP response element-binding protein (CREB) has been shown to mediate transcriptional activation of genes in response to both cAMP and calcium influx signal transduction pathways. The roles of two multifunctional calcium/calmodulin-dependent protein kinases, CaMKIV and CaMKII, were examined in transient transfection studies that utilized either the full-length or the constitutively active forms of these kinases. The results indicate that CaMKIV is much more potent than CaMKII in activating CREB in three different cell lines. It was also found in these studies that Ser133 of CREB is essential for its activation by CaMKIV. Because both CaMKII and CaMKIV can phosphorylate CREB, we pursued further the mechanism by which CaMKII and CaMKIV differentially regulate CREB activity. Mutagenesis studies and phosphopeptide mapping analysis demonstrated that in vitro, CaMKIV phosphorylates CREB at Ser133 only, whereas CaMKII phosphorylates CREB at Ser133 and a second site, Ser142. Transient transfection studies revealed that phosphorylation of Ser142 by CaMKII blocks the activation of CREB that would otherwise occur when Ser133 is phosphorylated. When Ser142 was mutated to alanine, CREB was activated by CaMKII, as well as by CaMKIV. Furthermore, mutation of Ser142 to alanine enhanced the ability of Ca2+ influx to activate CREB, suggesting a physiological role for the phosphorylation of Ser142 in modulation of CREB activity. These data provide evidence for a new mechanism for regulation of CREB activity involving phosphorylation of a negative regulatory site in the transcriptional activation domain. The studies also provide new insights into possible interactions between the cAMP and Ca2+ signaling pathways in the regulation of transcription. In particular, changes in intracellular Ca2+ have the potential to either inhibit or augment the ability of cAMP to stimulate transcription, depending on the presence of specific forms of Ca2+/calmodulin-dependent protein kinases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0890-9369
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2527-39
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:7958915-Amino Acid Sequence, pubmed-meshheading:7958915-Animals, pubmed-meshheading:7958915-Calcium, pubmed-meshheading:7958915-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:7958915-Cell Line, pubmed-meshheading:7958915-Cercopithecus aethiops, pubmed-meshheading:7958915-Consensus Sequence, pubmed-meshheading:7958915-Cyclic AMP, pubmed-meshheading:7958915-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:7958915-Isoenzymes, pubmed-meshheading:7958915-Kidney, pubmed-meshheading:7958915-Molecular Sequence Data, pubmed-meshheading:7958915-Mutagenesis, Site-Directed, pubmed-meshheading:7958915-PC12 Cells, pubmed-meshheading:7958915-Peptide Mapping, pubmed-meshheading:7958915-Phosphopeptides, pubmed-meshheading:7958915-Phosphorylation, pubmed-meshheading:7958915-Rats, pubmed-meshheading:7958915-Recombinant Proteins, pubmed-meshheading:7958915-Serine, pubmed-meshheading:7958915-Signal Transduction, pubmed-meshheading:7958915-Transcription, Genetic, pubmed-meshheading:7958915-Transfection
pubmed:year
1994
pubmed:articleTitle
Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity.
pubmed:affiliation
Department of Cell Biology and Anatomy, Oregon Health Sciences University, Portland 97201.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't