Neurotensin negatively modulates Akt activity in neurotensin receptor-1-transfected AV12 cells
| Autor: | Binhui Ni, Melvyn Baez, Feng Liu, Peiyi Yang |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cholera Toxin
Neurotensin receptor 1 Protein Serine-Threonine Kinases Biology Transfection Biochemistry Dephosphorylation Insulin Antagonists chemistry.chemical_compound Epidermal growth factor Cell Line Tumor Cricetinae Proto-Oncogene Proteins Heterotrimeric G protein Animals Humans Insulin Receptors Neurotensin Phosphorylation Protein Kinase Inhibitors Molecular Biology Protein kinase B Neurotensin PI3K/AKT/mTOR pathway G protein-coupled receptor Sulfonamides Epidermal Growth Factor Cell Biology Isoquinolines Molecular biology Enzyme Activation Pertussis Toxin chemistry Proto-Oncogene Proteins c-akt Protein Binding |
| Zdroj: | Journal of Cellular Biochemistry. 92:603-611 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | Neurotensin (NT) regulates a variety of biological processes primarily through interaction with neurotensin receptor-1 (NTR1), a heterotrimeric G-protein-coupled receptor (GPCR). Stimulation of NTR1 has been linked to activation of multiple signaling transduction pathways via specific coupling to G(q), G(i/o), or G(s), in various cell systems. However, the function of NT/NTR1 in the regulation of the Akt pathway remains unknown. Here, we report that activation of NTR1 by NT inhibits Akt activity as determined by the dephosphorylation of Akt at both Ser473 and Thr308 in AV12 cells constitutively expressing human NTR1 (NTR1/AV12). The inactivation of Akt by NT was rapid and dose-dependent. This effect of NT was completely blocked by the specific NTR1 antagonist, (S)-(+)-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)-carbonylamino] cyclohexylacetic acid (SR 48527), but unaffected by the less active enantiomer ((R)-(-)-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)-carbonylamino] cyclohexylacetic acid (SR 49711)), indicating the stereospecificity of NTR1 in the negative regulation of Akt. In addition, NT prevented insulin- and epidermal growth factor (EGF)-mediated Akt activation. Our results provide insight into the role of NT in the modulation of Akt signaling and the potential physiological significance of Akt regulation by NT. |
| Databáze: | OpenAIRE |
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