DEP-Domain-Mediated Regulation of GPCR Signaling Responses
Public Deposited- Creator
- Ballon, Daniel R.
- Flanary, Paul L.
- Gladue, Douglas P.
- Konopka, James B.
- Dohlman, Henrik G.
- Thorner, Jeremy
- Abstract
- 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.
- Date of publication
- 2006
- Keyword
- DOI
- Identifier
- Publisher DOI: https://doi.org/10.1016/j.cell.2006.07.030
- Onescience id: b18e4d13d9469f0859de10bd95084fab88671dbc
- Resource type
- Article
- Rights statement
- In Copyright
- Journal title
- Cell
- Journal volume
- 126
- Journal issue
- 6
- Language
- English
- ISSN
- 0092-8674
- 1097-4172
Relations
- Parents:
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