GABAB 受体亚基 GB1 在细胞表面通过 IGF-1R 的反式激活独立激活 ERK1/2。
GABAB receptor subunit GB1 at the cell surface independently activates ERK1/2 through IGF-1R transactivation.
机构信息
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.
出版信息
PLoS One. 2012;7(6):e39698. doi: 10.1371/journal.pone.0039698. Epub 2012 Jun 28.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: Our data suggest that GB1 may form a functional receptor at the cell surface in the absence of GB2.
背景
功能性 GABA(B) 受体被认为需要 GABA(B1) (GB1) 和 GABA(B2) (GB2) 亚基之间的异二聚化。GB1 细胞外结构域是配体结合所必需的，而 GB2 跨膜结构域负责与 G 蛋白偶联。在 GB2 缺陷型小鼠中观察到的非典型 GABA(B) 受体反应表明，GB1 可能在没有 GB2 的情况下具有活性。然而，其潜在机制仍知之甚少。
方法/主要发现：在这里，我们通过使用在没有 GB2 的情况下能够易位到细胞表面的 GB1 突变体（GB1asa）过表达的细胞，表明 GABA(B) 受体激动剂，如 GABA 和巴氯芬，在没有 GB2 的情况下可以诱导 ERK1/2 磷酸化。此外，我们证明 GB1asa 通过 Gi/o 蛋白和 PLC 依赖性 IGF-1R 转激活诱导 ERK1/2 磷酸化。
结论/意义：我们的数据表明，GB1 可能在没有 GB2 的情况下在细胞表面形成功能性受体。
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