1. The dopamine D4 receptor activates intracellular platelet-derived growth factor receptor β to stimulate ERK1/2
- Author
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Gill, Robin S., Hsiung, Marilyn S., Sum, Chi S., Lavine, Natalie, Clark, Stewart D., and Van Tol, Hubert H.M.
- Subjects
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DOPAMINE receptors , *PLATELET-derived growth factor , *ACTIVATION (Chemistry) , *G proteins , *GLYCOSYLATION , *TUNICAMYCIN - Abstract
Abstract: Dopamine receptors are GPCRs that play important roles in locomotion, reward, and cognitive processes. Previously, we demonstrated that this receptor transactivates PDGFRβ to modulate ERK1/2 and NMDA receptor activity. Downregulation of maturely glycosylated PDGFRβ by prolonged exposure to PDGF-BB eliminated PDGF-BB-mediated ERK1/2 activation. The DRD4-mediated ERK1/2 response was only partially blunted by PDGF-BB-mediated downregulation, but remained sensitive to the PDGFRβ kinase inhibitor tyrphostin A9. Tunicamycin prevented the N-linked glycosylation and maturation of PDGFRβ as well as its activation by PDGF-BB. However, upon tunicamycin treatment, DRD4 continued to signal to ERK1/2 in a tyrphostin A9-sensitive manner. Collectively, our observations indicate that DRD4, unlike PDGF-BB, can activate a pool of intracellularly located PDGFRβ. [Copyright &y& Elsevier]
- Published
- 2010
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