title: Expression of G protein-coupled receptor kinase 4 is associated with breast cancer tumourigenesis.
abstract: 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.
authors.affiliation: Department of Diagnostic Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Matsubayashi
authors.forename: M
authors.initials: M
authors.lastname: Takanashi
authors.forename: K
authors.initials: K
authors.lastname: Oikawa
authors.forename: K
authors.initials: K
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.forename: A
authors.initials: A
authors.lastname: De Blasi
authors.forename: M
authors.initials: M
authors.lastname: Bouvier
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
authors.forename: M
authors.initials: M
authors.lastname: Kuroda
authors.forename: K
authors.initials: K
authors.lastname: Mukai