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

Abstract：

: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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Coglievina M,Guarnaccia C,Zlatev V,Pongor S,Pintar A

doi

10.1016/j.bbrc.2013.02.022

subject

Has Abstract

pub_date

2013-03-22 00:00:00

pages

666-71

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)00267-2

journal_volume

432

pub_type

杂志文章

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