Abstract
Proteins that bind to G protein-coupled receptors have been identified as regulators of receptor localization and signaling. In our previous studies, a cytoskeletal protein, actin-binding protein 280 (ABP-280), was found to associate with the third cytoplasmic loop of dopamine D2 receptors. In this study, we demonstrate that ABP-280 also interacts with dopamine D3 receptors, but not with D4 receptors. Similar to the dopamine D2 receptor, the D3/ABP-280 association is of signaling importance. In human melanoma M2 cells lacking ABP-280, D3 receptors were unable to inhibit forskolin-stimulated cyclic AMP (cAMP) production significantly. D4 receptors, however, exhibited a similar degree of inhibition of forskolin-stimulated cAMP production in ABP-280-deficient M2 cells and ABP-280-replent M2 subclones (A7 cells). Further experiments revealed that the D3/ABP-280 interaction was critically dependent upon a 36 amino acid carboxyl domain of the D3 receptor third loop, which is conserved in the D2 receptor but not in the D4 receptor. Our results demonstrate a subtype-specific regulation of dopamine D2-family receptor signaling by the cytoskeletal protein ABP-280.
Original language | English (US) |
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Pages (from-to) | 859-863 |
Number of pages | 5 |
Journal | Biochemical Pharmacology |
Volume | 63 |
Issue number | 5 |
DOIs | |
State | Published - Mar 1 2002 |
Keywords
- Actin-binding protein 280
- Dopamine
- G protein-coupled receptor
- Protein interaction
- Receptor subtypes
- Signaling
ASJC Scopus subject areas
- Biochemistry
- Pharmacology