SDF-1α/CXCR4 Signaling in Lipid Rafts Induces Platelet Aggregation via PI3 Kinase-Dependent Akt Phosphorylation
| Autor: | Tomohiro Iguchi, Moyuru Hayashi, Kohji Kasahara, Naomasa Yamamoto, Kazuko Iida, Morio Arai, Yuichi Koike, Takahiko Hara, Motoyuki Shimonaka, Mizuho Kaneda, Hiroko Ohtsuka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Sucrose Platelet Aggregation Physiology lcsh:Medicine AKT2 Disaccharides Biochemistry Phosphatidylinositol 3-Kinases Cell Signaling Animal Cells Immune Physiology Medicine and Health Sciences Phosphorylation lcsh:Science Multidisciplinary Immune System Proteins Chemistry Organic Compounds Hematology Lipids Cell biology Body Fluids Blood Lipid Signaling Physical Sciences Anatomy Cellular Types Research Article Signal Transduction Platelets Blood Platelets Receptors CXCR4 Immunology Carbohydrates Antibodies 03 medical and health sciences Membrane Microdomains Humans Platelet activation Protein kinase B Blood Coagulation PI3K/AKT/mTOR pathway Blood Cells Akt/PKB signaling pathway lcsh:R Organic Chemistry Chemical Compounds Membrane raft Biology and Life Sciences Proteins Lipid signaling Cell Biology Platelet Activation Chemokine CXCL12 Monoclonal Antibodies G-Protein Signaling 030104 developmental biology lcsh:Q Proto-Oncogene Proteins c-akt |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 1, p e0169609 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Stromal cell-derived factor-1α (SDF-1α)-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and phosphatidylinositol 3 kinase (PI3K). Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in human platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α also induces the phosphorylation of PDK1 at Ser241 (an upstream activator of Akt), GSK3β at Ser9 (a downstream substrate of Akt), and myosin light chain at Ser19 (a downstream element of the Akt signaling pathway). SDF-1α-induced platelet aggregation is inhibited by pretreatment with the Akt inhibitor MK-2206 in a dose-dependent manner. Furthermore, SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the raft-disrupting agent methyl-β-cyclodextrin. Sucrose density gradient analysis shows that 35% of CXCR4, 93% of the heterotrimeric G proteins Gαi-1, 91% of Gαi-2, 50% of Gβ and 4.0% of PI3Kβ, and 4.5% of Akt2 are localized in the detergent-resistant membrane raft fraction. These findings suggest that SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3K-dependent Akt phosphorylation. |
| Databáze: | OpenAIRE |
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