Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-9-22
pubmed:abstractText
G protein-coupled receptors (GPCRs) mediate cellular responses to a variety of stimuli, but how specific responses are regulated has been elusive, as the types of GPCRs vastly outnumber the classes of G protein heterotrimers available to initiate downstream signaling. In our analysis of signaling proteins containing DEP domains ( approximately 90 residue sequence motifs first recognized in fly Dishevelled, worm EGL-10, and mammalian Pleckstrin), we find that DEP domains are responsible for specific recognition of GPCRs. We examined the yeast regulator of G protein signaling (RGS) protein Sst2 and demonstrate that the DEP domains in Sst2 mediate binding to its cognate GPCR (Ste2). DEP-domain-mediated tethering promotes downregulation by placing the RGS protein in proximity to its substrate (receptor-activated Galpha subunit). Sst2 docks to the Ste2 cytosolic tail, but only its unphosphorylated state, allowing for release and recycling of this regulator upon receptor desensitization and internalization. DEP-domain-mediated targeting of effectors and regulators to specific GPCRs provides a means to dictate the nature, duration, and specificity of the response.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0092-8674
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1079-93
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16990133-Amino Acid Sequence, pubmed-meshheading:16990133-Cytosol, pubmed-meshheading:16990133-Down-Regulation, pubmed-meshheading:16990133-GTPase-Activating Proteins, pubmed-meshheading:16990133-Models, Biological, pubmed-meshheading:16990133-Molecular Sequence Data, pubmed-meshheading:16990133-Phosphorylation, pubmed-meshheading:16990133-Protein Binding, pubmed-meshheading:16990133-Protein Structure, Tertiary, pubmed-meshheading:16990133-Protein Subunits, pubmed-meshheading:16990133-Receptors, G-Protein-Coupled, pubmed-meshheading:16990133-Receptors, Mating Factor, pubmed-meshheading:16990133-Saccharomyces cerevisiae, pubmed-meshheading:16990133-Saccharomyces cerevisiae Proteins, pubmed-meshheading:16990133-Sequence Homology, Amino Acid, pubmed-meshheading:16990133-Signal Transduction
pubmed:year
2006
pubmed:articleTitle
DEP-domain-mediated regulation of GPCR signaling responses.
pubmed:affiliation
Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural