Jagged-1 juxtamembrane region: biochemical characterization and cleavage by ADAM17 (TACE) catalytic domain.

摘要: Ectodomain shedding of membrane receptors and ligands carried out by ADAMs (A disintegrin metalloprotease) plays a major role in several signaling pathways, including Notch. The grounds substrate recognition, however, are poorly understood. We demonstrate that recombinant protein corresponding to the juxtamembrane region Jagged-1, one Notch ligands, behaves as structured module is cleaved ADAM17 catalytic domain at E1054. A short synthetic peptide same site but much higher rate, implying structure cleavage native key determinant for recognition. also show an Alagille syndrome-associated mutation near E1054 increases which suggests this may lead unbalance due level Jagged-1 shedding.