RGD Reference Report - Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites.

Authors: Ragusa, Michael J  Dancheck, Barbara  Critton, David A  Nairn, Angus C  Page, Rebecca  Peti, Wolfgang 
Citation: Ragusa MJ, etal., Nat Struct Mol Biol. 2010 Apr;17(4):459-64. doi: 10.1038/nsmb.1786. Epub 2010 Mar 21.
RGD ID: 13432348
Pubmed: PMID:20305656   (View Abstract at PubMed)
PMCID: PMC2924587   (View Article at PubMed Central)
DOI: DOI:10.1038/nsmb.1786   (Journal Full-text)

The serine/threonine protein phosphatase 1 (PP1) dephosphorylates hundreds of key biological targets. PP1 associates with >or=200 regulatory proteins to form highly specific holoenzymes. These regulatory proteins target PP1 to its point of action within the cell and prime its enzymatic specificity for particular substrates. However, how they direct PP1's specificity is not understood. Here we show that spinophilin, a neuronal PP1 regulator, is entirely unstructured in its unbound form, and it binds PP1 through a folding-upon-binding mechanism in an elongated fashion, blocking one of PP1's three putative substrate binding sites without altering its active site. This mode of binding is sufficient for spinophilin to restrict PP1's activity toward a model substrate in vitro without affecting its ability to dephosphorylate its neuronal substrate, glutamate receptor 1 (GluR1). Thus, our work provides the molecular basis for the ability of spinophilin to dictate PP1 substrate specificity.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ppp1r9aRatprotein binding enablesIPIUniProtKB:P62136PMID:20305656IntAct 
Ppp1r9bRatprotein binding enablesIPIUniProtKB:P62136PMID:20305656IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Ppp1r9a  (protein phosphatase 1, regulatory subunit 9A)
Ppp1r9b  (protein phosphatase 1, regulatory subunit 9B)


Additional Information