title: Serine 133 phosphorylation is not required for hippocampal CREB-mediated transcription and behavior.
abstract: The cAMP response element (CRE)-binding protein, CREB, is a transcription factor whose activity in the brain is critical for long-term memory formation. Phosphorylation of Ser133 in the kinase-inducible domain (KID), that in turn leads to the recruitment of the transcriptional coactivator CREB-binding protein (CBP), is thought to mediate the activation of CREB. However, the importance of phosphorylation for CREB binding to DNA and subsequent gene transcription in vivo is controversial. To definitively address the role of CREB phosphorylation in gene transcription and learning and memory, we derived mutant mice lacking the Ser133 phosphorylation site. These mice exhibit normal CREB-mediated gene transcription for a number of genes implicated in learning and memory processes. Furthermore these mice have no deficits in hippocampus- or striatum-dependent learning. Strikingly, our findings show that CREB phosphorylation at Ser133 is not necessary for CREB binding to CRE sites, CREB-mediated transcription, or CREB-mediated behavioral phenotypes associated with learning and memory.
authors.affiliation: Department of Psychology, Temple University, Philadelphia, Pennsylvania 19122, USA.
authors.forename: Lisa A
authors.identifier: http://orcid.org/0000-0002-1228-5061
authors.initials: LA
authors.lastname: Briand
authors.affiliation: Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Bridgin G
authors.initials: BG
authors.lastname: Lee
authors.affiliation: Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lelay
authors.affiliation: Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.affiliation: Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA blendy@mail.med.upenn.edu.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Blendy
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D012694:Serine / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D012694:Serine