Biomaterial Database

Phosphorylation of cyclic adenosine 3',5'-monophosphate (cAMP) response element-binding protein isoforms by the cAMP-dependent protein kinase. 1992

P Sun, and W E Schoderbek, and R A Maurer

Department of Physiology and Biophysics, University of Iowa, Iowa City 52242.

The cAMP response element-binding protein (CREB) mediates transcriptional activation of genes in response to the cAMP signal transduction pathway. There are two different isoforms of CREB, which are generated by alternative RNA splicing. There is evidence that the two isoforms may have different biological activities. As the longer isoform (CREB341) contains a potential phosphorylation site that is not present in the shorter isoform (CREB327), we examined the possible differential phosphorylation of the two CREB isoforms. Recombinant CREB was prepared and used as substrate for phosphorylation by the cAMP-dependent protein kinase in vitro. Phosphopeptide mapping and mutagenesis studies demonstrated that CREB341 contains two sites, serine 133 and serine 98, that can be phosphorylated in vitro by the catalytic subunit of the cAMP-dependent protein kinase. In contrast, CREB327 contains only a single phosphorylation site at serine 119 (equivalent position to serine 133 in CREB341). A kinase titration experiment demonstrated that serine 98 of CREB341 was phosphorylated only at relatively high concentrations of the cAMP-dependent protein kinase. Transient transfection studies were used to test for any possible function of the phosphorylation of serine 98 of CREB341. These studies used GAL4-CREB fusion proteins. We found that mutation of serine 98 to alanine (which would block phosphorylation) has little or no effect on the ability of the CREB fusion protein to activate transcription. These findings suggest that differences in the biological activity of the two CREB isoforms are probably not mediated by differential phosphorylation by the cAMP-dependent protein kinase.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D010768	Phosphoserine	The phosphoric acid ester of serine.	Serine Phosphate,Phosphorylserine,Seryl Phosphate,Phosphate, Serine,Phosphate, Seryl
D011494	Protein Kinases	A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.	Protein Kinase,Kinase, Protein,Kinases, Protein
D011499	Protein Processing, Post-Translational	Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.	Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012326	RNA Splicing	The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.	RNA, Messenger, Splicing,Splicing, RNA,RNA Splicings,Splicings, RNA
D016297	Mutagenesis, Site-Directed	Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.	Mutagenesis, Oligonucleotide-Directed,Mutagenesis, Site-Specific,Oligonucleotide-Directed Mutagenesis,Site-Directed Mutagenesis,Site-Specific Mutagenesis,Mutageneses, Oligonucleotide-Directed,Mutageneses, Site-Directed,Mutageneses, Site-Specific,Mutagenesis, Oligonucleotide Directed,Mutagenesis, Site Directed,Mutagenesis, Site Specific,Oligonucleotide Directed Mutagenesis,Oligonucleotide-Directed Mutageneses,Site Directed Mutagenesis,Site Specific Mutagenesis,Site-Directed Mutageneses,Site-Specific Mutageneses