Journal
BIOCHEMICAL PHARMACOLOGY
Volume 63, Issue 5, Pages 859-863Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0006-2952(01)00932-7
Keywords
dopamine; G protein-coupled receptor; protein interaction; actin-binding protein 280; receptor subtypes; signaling
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Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH [R29MH057889] Funding Source: NIH RePORTER
- NIMH NIH HHS [MH57889] Funding Source: Medline
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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 D-2 receptors. In this study, we demonstrate that ABP-280 also interacts with dopamine D-3 receptors, but not with D-4 receptors. Similar to the dopamine D-2 receptor, the D-3/ABP-280 association is of signaling importance. In human melanoma M2 cells lacking ABP-280. D-3 receptors were unable to inhibit forskolin-stimulated cyclic AMP (CAMP) production significantly. D-4 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 D-3/ABP-280 interaction was critically dependent upon a 36 amino acid carboxyl domain of the D-3 receptor third loop, which is conserved in the D-2 receptor but not in the D-4 receptor. Our results demonstrate a subtype-specific regulation of dopamine D-2-family receptor signaling by the cytoskeletal protein ABP-280. (C) 2002 Elsevier Science Inc. All rights reserved.
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