title: GABAB receptor subunit GB1 at the cell surface independently activates ERK1/2 through IGF-1R transactivation.
abstract: BACKGROUND
  Functional GABA(B) receptor is believed to require hetero-dimerization between GABA(B1) (GB1) and GABA(B2) (GB2) subunits. The GB1 extracellular domain is required for ligand binding, and the GB2 trans-membrane domain is responsible for coupling to G proteins. Atypical GABA(B) receptor responses observed in GB2-deficient mice suggested that GB1 may have activity in the absence of GB2. However the underlying mechanisms remain poorly characterized.
  
  
  RESULTS
  Here, by using cells overexpressing a GB1 mutant (GB1asa) with the ability to translocate to the cell surface in the absence of GB2, we show that GABA(B) receptor agonists, such as GABA and Baclofen, can induce ERK1/2 phosphorylation in the absence of GB2. Furthermore, we demonstrate that GB1asa induces ERK1/2 phosphorylation through Gi/o proteins and PLC dependent IGF-1R transactivation.
  
  
  CONCLUSIONS
  Our data suggest that GB1 may form a functional receptor at the cell surface in the absence of GB2.
authors: Sino-France Laboratory for Drug Screening, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: Guillaume A
authors: GA
authors: Baloucoune
authors: Lei
authors: L
authors: Chun
authors: Wenhua
authors: W
authors: Zhang
authors: Chanjuan
authors: C
authors: Xu
authors: Siluo
authors: S
authors: Huang
authors: Qian
authors: Q
authors: Sun
authors: Yunyun
authors: Y
authors: Wang
authors: Haijun
authors: H
authors: Tu
authors: Jianfeng
authors: J
authors: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D018080:Receptors, GABA-B / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D017931:DNA Primers; D018080:Receptors, GABA-B; D017526:Receptor, IGF Type 1