The dopamine D4 receptor activates intracellular platelet-derived growth factor receptor beta to stimulate ERK1/2.

Dopamine receptors are GPCRs that play important roles in locomotion, reward, and cognitive processes. Previously, we demonstrated that this receptor transactivates PDGFRbeta to modulate ERK1/2 and NMDA receptor activity. Downregulation of maturely glycosylated PDGFRbeta 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 PDGFRbeta kinase inhibitor tyrphostin A9. Tunicamycin prevented the N-linked glycosylation and maturation of PDGFRbeta 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 PDGFRbeta.