Cell Signal. 2010 Feb;22(2):285-90. Epub 2009 Sep 24.

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

Gill RS, Hsiung MS, Sum CS, Lavine N, Clark SD, Van Tol HH.

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Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Abstract

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.

PMID:: 19782129; [PubMed - indexed for MEDLINE]

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Research Support, Non-U.S. Gov't

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Canadian Institutes of Health Research/Canada

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Cited by 1 PubMed Central article

Transactivation of PDGFRbeta by dopamine D4 receptor does not require PDGFRbeta dimerization. [Mol Brain. 2010]
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