| Autor: |
Tadokoro, Seiji, Tomiyama, Yoshiaki, Honda, Shigenori, Kashiwagi, Hirokazu, Kosugi, Satoru, Shiraga, Masamichi, Kiyoi, Teruo, Kurata, Yoshiyuki, Matsuzawa, Yuji |
| Zdroj: |
Blood; February 2002, Vol. 99 Issue: 3 p931-938, 8p |
| Abstrakt: |
αIIbβ3and αvβ3belong to the β3integrin subfamily. Although the β3subunit is a key regulator for the biosynthesis of β3integrins, it remains obscure whether missense mutations in β3may induce the same defects in both αIIbβ3and αvβ3. In this study, it is revealed that thrombasthenic platelets with a His280Pro mutation in β3, which is prevalent in Japanese patients with Glanzmann thrombasthenia, did contain significant amounts of αvβ3(about 50% of control) using sensitive enzyme-linked immunosorbent assay. Expression studies showed that the His280Proβ3mutation impaired αIIbβ3expression but not αvβ3expression in 293 cells. To extend these findings, the effects of several β3missense mutations leading to an impaired αIIbβ3expression on αvβ3function as well as expression was examined: Leu117Trp, Ser162Leu, Arg216Gln, Cys374Tyr, and a newly created Arg216Gln/Leu292Ser mutation. Leu117Trp and Cys374Tyr β3mutations did impair αvβ3expression, while Ser162Leu, Arg216Gln, and Arg216Gln/Leu292Ser mutations did not. With regard to ligand binding function, Ser162Leu mutation induced especially distinct effects between 2 β3integrins: it markedly impaired ligand binding to αIIbβ3but not to αvβ3at all. These data clearly demonstrate that the biosynthesis and the ligand binding function of αIIbβ3and those of αvβ3are regulated in part by different mechanisms. Present data would be a clue to elucidate the regulatory mechanism of expression and function of β3integrins. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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