کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1928830 | 1050427 | 2013 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Jagged-1 juxtamembrane region: Biochemical characterization and cleavage by ADAM17 (TACE) catalytic domain Jagged-1 juxtamembrane region: Biochemical characterization and cleavage by ADAM17 (TACE) catalytic domain](/preview/png/1928830.png)
Ectodomain shedding of membrane receptors and ligands carried out by ADAMs (A disintegrin and metalloprotease) plays a major role in several signaling pathways, including Notch. The grounds of substrate recognition, however, are poorly understood. We demonstrate that a recombinant protein corresponding to the juxtamembrane region of Jagged-1, one of the Notch ligands, behaves as a structured module and is cleaved by ADAM17 catalytic domain at E1054. A short synthetic peptide is cleaved at the same site but at a much higher rate, implying that the structure of the cleavage site in the native protein is a key determinant for substrate recognition. We also show that an Alagille syndrome-associated mutation near E1054 increases the cleavage rate, which suggests that this mutation may lead to an unbalance in Notch signaling due to a higher level of Jagged-1 shedding.
► The juxtamembrane region of Jagged-1 is a structured domain.
► Jagged-1 juxtamembrane domain is cleaved at E1054 by ADAM17 catalytic domain.
► The protein native environment determines cleavage rate.
► Jagged-1 VR→G mutation associated with Alagille syndrome affects the cleavage rate.
Journal: Biochemical and Biophysical Research Communications - Volume 432, Issue 4, 22 March 2013, Pages 666–671