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A point mutation in the integrin beta 3 cytoplasmic domain (S752-->P) impairs bidirectional signaling through alpha IIb beta 3 (platelet glycoprotein IIb-IIIa)
| Content Provider | Scilit |
|---|---|
| Author | O'Toole, Te Chen, Yp Ylanne, J. Rosa, Jp Ginsberg, Mh |
| Copyright Year | 1994 |
| Description | 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. |
| Related Links | https://ashpublications.org/blood/article-pdf/84/6/1857/615879/1857.pdf |
| Ending Page | 1865 |
| Page Count | 9 |
| Starting Page | 1857 |
| DOI | 10.1182/blood.v84.6.1857.1857 |
| Journal | Blood |
| Issue Number | 6 |
| Volume Number | 84 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1994-09-15 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry and Molecular Biology Glycoprotein S752 Cytoplasmic Domain Alpha Iib Beta Journal: Blood (Vol- 89, Issue- 6) |
| Content Type | Text |
| Resource Type | Article |
