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Mitigation of Blood Borne Cell Attachment to Metal Implants through CD47-Derived Peptide Immobilization
Published on: December 3, 2020
The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi
W A Frazier1, A G Gao, J Dimitry
1Departments of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. frazier@biochem.wustl.edu
The Journal of Biological Chemistry
|March 20, 1999
Summary
Integrin-associated protein (CD47) forms a complex with beta3 integrins and Gi proteins, mediating cell signaling. This interaction explains CD47
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Integrin-associated protein (IAP), also known as CD47, acts as a thrombospondin receptor.
- CD47 forms signaling complexes with beta3 integrins, influencing cell functions like spreading and chemotaxis.
- These CD47-mediated effects are sensitive to pertussis toxin, suggesting involvement of Gi proteins.
Purpose of the Study:
- To investigate the molecular mechanism underlying CD47-mediated signaling.
- To determine if CD47 directly interacts with heterotrimeric G proteins.
- To elucidate the role of Gi proteins in CD47's biological functions.
Main Methods:
- Immunoprecipitation and affinity chromatography to isolate protein complexes.
- GTP and AlF4 treatment to assess protein interactions and G protein activation.
- Binding assays using agonist peptide (4N1K) and radiolabeled GTP (GTPgamma35S).
Main Results:
- CD47, beta3 integrins, and Gi proteins form a stable, detergent-soluble complex.
- Gialpha subunit dissociates from the complex upon GTP or AlF4 treatment.
- The agonist peptide 4N1K reduces CD47 binding to Gi and decreases intraplatelet cyclic AMP levels.
- 4N1K stimulates GTPgamma35S binding to membranes expressing CD47 and alphavbeta3.
Conclusions:
- CD47 functionally couples to heterotrimeric G proteins, specifically Gi.
- This interaction provides a mechanistic basis for CD47's diverse biological roles.
- The findings reveal a novel signaling pathway involving CD47 and Gi proteins.
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