Journal
JOURNAL OF PATHOLOGY
Volume 216, Issue 3, Pages 317-327Publisher
WILEY
DOI: 10.1002/path.2414
Keywords
GRK4; beta-arrestin; breast cancer; GPCR; MAPK
Funding
- Ministry of Education, culture, Sports, Science and Technology (MEXT) of Japan
- Ministry of Health, Labour and Welfare of Japan
- Japan Health Sciences Foundation
- Yamaguchi Endocrine Research Association
- University-Industry Joint Research Project
- Tokyo Medical University Cancer Research Foundation
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G-protein-coupled receptor kinases (GRKs) comprise a family of seven mammalian serine/threonine protein kinases that phosphorylate and regulate agonist-bound, activated, G-protein-coupled receptors (GPCRs). GRKs and beta-arrestins are key participants in the canonical pathways leading to phosphorylation-dependent GPCR desensitization, endocytosis, intracellular trafficking and resensitization. Here we show, that GRK4 isoforms are expressed in human breast cancer but not in normal epithelia. In addition, GRK4-over-expressing cells activated the mitogen-activated protein kinase (MAPK) mediated by ERK 1/2 and JNK phosphorylation in breast cancer-derived cell lines. Furthermore, suppression of beta-arrestins decreased GRM-stimulated ERK 1/2 or JNK phosphorylations. These data indicate that high-level expression of GRK4 may activate MAPK signalling pathways mediated by beta-arrestins in breast cancer cells, suggesting that GRK4 may be implicated in breast cancer carcinogenesis. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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