D1 Dopamine Receptor Phosphorylation Assays
The dopamine D1 receptor belongs to the D1-like subfamily of dopamine receptors. It stimulates cAMP production by coupling to stimulatory G proteins. The classical view of dopamine receptor signaling implies that the D1 receptor stimulates the cAMP/PKA/DARPP-32 pathway. Moreover, D1 receptor-mediated PKA activation also results in the activation of the extracellular signal-regulated kinases 1/2 (Erk1/2) by two mechanisms: src-Shp2-dependent Erk1/2 phosphorylation and DARPP-32-mediated inhibition of protein phosphatase-1. It is believed that upregulation of these mechanisms, leading to aberrant Erk1/2 activation, are involved in the development of L-DOPA-induced dyskinesias in animal models of Parkinson’s disease. D1 desensitization, trafficking and signaling are regulated by phosphorylation of carboxyl-terminal threonine354 (pT354-D1), serine372/serine373 (pS372/pS373-D1). This nomenclature refers to the human D1. This phosphorylation motif is also present in mice and rats. For more information on D1 receptor pharmacology please refer to the IUPHAR database. For further reading refer to:
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Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 2011 Mar;63(1):182-217. doi: 10.1124/pr.110.002642. Epub 2011 Feb 8. PMID: 21303898.
Beaulieu JM, Espinoza S, Gainetdinov RR. Dopamine receptors - IUPHAR Review 13. Br J Pharmacol. 2015 Jan;172(1):1-23. doi: 10.1111/bph.12906. PMID: 25671228; PMCID: PMC4280963.