A point mutation in the integrin beta 3 cytoplasmic domain (S752-->P) impairs bidirectional signaling through alpha IIb beta 3 (platelet glycoprotein IIb-IIIa)
| Autoři: | Yp, Chen, Toole Te, O., Jari Ylänne, Jp, Rosa, Mh, Ginsberg |
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| Zdroj: | Europe PubMed Central |
| Témata: | Cytoplasm, Integrins, Integrin beta3, Fibrinogen, CHO Cells, Platelet Membrane Glycoproteins, Transfection, Cricetinae, Cell Adhesion, Microscopy, Electron, Scanning, Animals, Humans, Point Mutation, Signal Transduction, Thrombasthenia |
| Popis: | Agonist-induced inside-out signaling results in an increased affinity of integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) for soluble ligands (fibrinogen [Fg] and PAC1). Ligand binding to integrins initiates outside-in signaling that leads to cellular responses such as cell spreading and focal adhesion formation. A point mutation in the beta 3 cytoplasmic domain (S752--P) is associated with blocked inside-out alpha IIb beta 3 signaling in a variant Glanzmann's thrombasthenia. This mutation was introduced into beta 3 and cotransfected into Chinese hamster ovary cells with a chimeric alpha subunit consisting of the alpha IIb extracellular and transmembrane domains and the alpha 6B cytoplasmic domain. The substitution of the alpha IIb cytoplasmic domain with that of alpha 6 led to activation of alpha IIb beta 3 to bind PAC1, mimicking inside-out signaling. This effect was reversed by the S752--P mutation, indicating a disruption of inside-out signaling by the mutation. In addition, transfectants expressing this beta 3 variant showed reduced alpha IIb beta 3-mediated cell spreading on immobilized Fg, focal adhesion, and fibrin clot retraction, suggesting an impairment in outside-in alpha IIb beta 3 signaling. Therefore, a single point mutation in the beta 3 cytoplasmic domain impaired bidirectional signaling through alpha IIb beta 3. |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::87543c6c5a3ba07be7d93091d635f124 http://europepmc.org/abstract/med/8080992 |
| Přírůstkové číslo: | edsair.pmid.dedup....87543c6c5a3ba07be7d93091d635f124 |
| Autor: | Yp, Chen, Toole Te, O., Jari Ylänne, Jp, Rosa, Mh, Ginsberg |
| Předmět: | |
| Zdroj: | Europe PubMed Central |
| Popis: | Agonist-induced inside-out signaling results in an increased affinity of integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) for soluble ligands (fibrinogen [Fg] and PAC1). Ligand binding to integrins initiates outside-in signaling that leads to cellular responses such as cell spreading and focal adhesion formation. A point mutation in the beta 3 cytoplasmic domain (S752--P) is associated with blocked inside-out alpha IIb beta 3 signaling in a variant Glanzmann's thrombasthenia. This mutation was introduced into beta 3 and cotransfected into Chinese hamster ovary cells with a chimeric alpha subunit consisting of the alpha IIb extracellular and transmembrane domains and the alpha 6B cytoplasmic domain. The substitution of the alpha IIb cytoplasmic domain with that of alpha 6 led to activation of alpha IIb beta 3 to bind PAC1, mimicking inside-out signaling. This effect was reversed by the S752--P mutation, indicating a disruption of inside-out signaling by the mutation. In addition, transfectants expressing this beta 3 variant showed reduced alpha IIb beta 3-mediated cell spreading on immobilized Fg, focal adhesion, and fibrin clot retraction, suggesting an impairment in outside-in alpha IIb beta 3 signaling. Therefore, a single point mutation in the beta 3 cytoplasmic domain impaired bidirectional signaling through alpha IIb beta 3. |
| Databáze: | OpenAIRE |
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