title: Intracellular and nuclear bradykinin B2 receptors.
abstract: Bradykinin is a vasoactive peptide that participates in numerous inflammatory processes, vasodilation, and cell growth/survival; it mainly acts through two receptor subtypes, bradykinin B1 and bradykinin B2 receptors, which are G protein-coupled receptor (GPCR) family members. Details on ubiquitin-dependent degradation via the lysosome and/or proteasome, and the recycling process that directs bradykinin B2 receptor to the cell surface after agonist-induced endocytosis remain unclear; nevertheless, intracellular localization and internalization of GPCRs following stimulation by ligands are well known. Evidence concerning the nuclear localization and functions of GPCRs has been accumulating. The bradykinin B2 receptor has been shown to localize in the nucleus and suggested to function as a transcriptional regulator of specific genes. The transfer of membrane GPCRs (regardless of liganding), including the bradykinin B2 receptor to the nucleus can be attributed to the presence of a peptide sequence referred to as the nuclear localization signal (NLS). More recently, we found that nuclear bradykinin B2 receptors form heterodimers with the nuclear lamina protein, lamin C. The function of heterodimerization of the bradykinin B2 receptor with lamin C is still unclear. However, nuclear proteins lamin A/C are involved in a variety of diseases. Although further studies are required to elucidate the precise functions and mechanisms of intracellular and nuclear bradykinin B2 receptors, here we discuss the role of lamin A/C in laminopathies and examine the clinical significance of the bradykinin B2 receptor heterodimer.
authors.affiliation: Laboratory of Molecular Cell Biology, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. Electronic address: takano@pharm.kobegakuin.ac.jp.
authors.forename: Masaoki
authors.initials: M
authors.lastname: Takano
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji 670-8524, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Matsuyama
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*
chemical_list: D043782:Receptor, Bradykinin B2; D018160:Receptors, Cytoplasmic and Nuclear
keywords: Bradykinin B(2) receptor; Internalization; Lamin C; Nuclear localization