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Expression of G protein-coupled receptor kinase 4 is associated with breast cancer tumourigenesis.

Matsubayashi J, Takanashi M, Oikawa K, Fujita K, Tanaka M, Xu M, De Blasi A, Bouvier M, Kinoshita M, Kuroda M, Mukai K

Department of Diagnostic Pathology, Tokyo Medical University, Tokyo, Japan.

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 GRK4-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.

J. Pathol. 2008;216(3):317-27.

Pubmed ID: 18767025

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