文献类型：会议

作　　者：涂海军 Philippe Rondard 许婵娟 刘剑峰

作者单位：华中科技大学生命科学与技术学院分子生物物理教育部重点实验室 Institut de Génomique Fonctionnelle (CNRS UMR5203,INSERM, U661) Département de Pharmacologie Moléculaire, 141Rue de la Cardonille,Montpellier F-34094 Cedex 5, France

会议文献：湖北省暨武汉市生物化学与分子生物学学会第八届第十七次学术年会论文汇编

会议名称：湖北省暨武汉市生物化学与分子生物学学会第八届第十七次学术年会

会议日期：20070600

会议地点：中国湖北宜昌

主办单位：湖北省暨武汉市生化与分子生物学学会

出版日期：20070600

学会名称：湖北省科学技术协会

语　　种：中文

摘　　要：γ-aminobutyric acid type B(GABAB)receptor is an aUosteric complex made of two subunits,GABAB1 and GABAB2.GABAB2 plays a major role in the coupling to G-protein whereas GABAB1 binds GABA.It has been shown that GABAB receptor activates ERK1/2 in neurons of the central nervous system,but the molecular mechanisms underlying this event are poorly characterized.Here,we demonstrate that activation of GABAB receptor by either GABA or the selective agonist baclofen induces ERK1/2 phosphorylation in cultured cerebellar granule neurons.We also show that CGP7930,a positive allosteric regulator specific of GABAB2,alone can induce the phosphorylation of ERK1/2.PTX,a Gi/o inhibitor,abolishes both baclofen and CGP7930-mediated ERK1/2 phosphorylation.Moreover,both baclofen and CGP7930 induce ERK-dependent CREB phosphorylation.Furthermore,by using LY294002,a PI-3 kinase inhibitor,and a C-term of GRK-2 that has been reported to sequester Gβγ subunits,we demonstrate the rote of Gβγ in GABAB receptor mediated-ERK1/2 phosphorylation.In conclusion,the activation of GABAB receptor leads to ERK1/2 phosphorylation via the coupling of GABAB2 to Gi/o and by releasing Gβγ subunits which in turn induce the activation of CREB.These findings suggest a role of GABAB receptor in long-term change in the central nervous system.

关 键 词：ERK  Dominant role of GABAB2 and G  for GABAB receptor mediated-ERK1/2/CREB pathway in cerebellar neurons  

分 类 号：Q42]