Inhibitory and Stimulatory Regulation of Rac and Cell Motility by the G<sub>12/13</sub>-Rho and G<sub>i</sub> Pathways Integrated Downstream of a Single G Protein-Coupled Sphingosine-1-Phosphate Receptor Isoform
-
- Naotoshi Sugimoto
- Department of Physiology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8640, Japan
-
- Noriko Takuwa
- Department of Physiology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8640, Japan
-
- Hiroyuki Okamoto
- Department of Physiology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8640, Japan
-
- Sotaro Sakurada
- Department of Physiology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8640, Japan
-
- Yoh Takuwa
- Department of Physiology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8640, Japan
説明
The G protein-coupled receptors S1P2/Edg5 and S1P3/Edg3 both mediate sphingosine-1-phosphate (S1P) stimulation of Rho, yet S1P2 but not S1P3 mediates downregulation of Rac activation, membrane ruffling, and cell migration in response to chemoattractants. Specific inhibition of endogenous Galpha12 and Galpha13, but not of Galphaq, by expression of respective C-terminal peptides abolished S1P2-mediated inhibition of Rac, membrane ruffling, and migration, as well as stimulation of Rho and stress fiber formation. Fusion receptors comprising S1P2 and either Galpha12 or Galpha13, but not Galphaq, mediated S1P stimulation of Rho and also inhibition of Rac and migration. Overexpression of Galphai, by contrast, specifically antagonized S1P2-mediated inhibition of Rac and migration. The S1P2 actions were mimicked by expression of V14Rho and were abolished by C3 toxin and N19Rho, but not Rho kinase inhibitors. In contrast to S1P2, S1P3 mediated S1P-directed, pertussis toxin-sensitive chemotaxis and Rac activation despite concurrent stimulation of Rho via G12/13. Upon inactivation of Gi by pertussis toxin, S1P3 mediated inhibition of Rac and migration just like S1P2. These results indicate that integration of counteracting signals from the Gi- and the G12/13-Rho pathways directs either positive or negative regulation of Rac, and thus cell migration, upon activation of a single S1P receptor isoform.
収録刊行物
-
- Molecular and Cellular Biology
-
Molecular and Cellular Biology 23 (5), 1534-1545, 2003-03-01
Informa UK Limited
- Tweet
キーワード
- rac1 GTP-Binding Protein
- rho GTP-Binding Proteins
- Botulinum Toxins
- Time Factors
- Recombinant Fusion Proteins
- Blotting, Western
- Receptors, Cell Surface
- CHO Cells
- GTP-Binding Protein alpha Subunits, Gi-Go
- Transfection
- GTP-Binding Protein alpha Subunits, G12-G13
- Culture Media, Serum-Free
- Adenoviridae
- Receptors, G-Protein-Coupled
- Mice
- Cell Movement
- Cricetinae
- Animals
- Protein Isoforms
- Cell Growth and Development
- Dose-Response Relationship, Drug
- Reverse Transcriptase Polymerase Chain Reaction
- Chemotaxis
- 3T3 Cells
- Heterotrimeric GTP-Binding Proteins
- rac GTP-Binding Proteins
- Microscopy, Fluorescence
- Pertussis Toxin
- Receptors, Lysophospholipid
- COS Cells
- Peptides
- Plasmids
- Signal Transduction
詳細情報 詳細情報について
-
- CRID
- 1362825895699207168
-
- NII論文ID
- 80015822008
-
- ISSN
- 10985549
-
- PubMed
- 12588974
-
- データソース種別
-
- Crossref
- CiNii Articles
- OpenAIRE