Skip to Content
Merck
  • GRP78 protects a disintegrin and metalloprotease 17 against protein-disulfide isomerase A6 catalyzed inactivation.

GRP78 protects a disintegrin and metalloprotease 17 against protein-disulfide isomerase A6 catalyzed inactivation.

FEBS letters (2017-09-28)
Miriam Schäfer, Daniela C Granato, Sebastian Krossa, Anne-Kathrin Bartels, Sami Yokoo, Stefan Düsterhöft, Tomas Koudelka, Axel J Scheidig, Andreas Tholey, Adriana F Paes Leme, Joachim Grötzinger, Inken Lorenzen
ABSTRACT

The shedding of ectodomains is a crucial mechanism in many physiological and pathological events. A disintegrin and metalloprotease-17 (ADAM17) is a key sheddase involved in essential processes, such as development, regeneration, and immune defense. ADAM17 exists in two conformations which differ in their disulfide connection in the membrane-proximal domain (MPD). Protein-disulfide isomerases (PDIs) on the cell surface convert the open MPD into a rigid closed form, which corresponds to inactive ADAM17. ADAM17 is expressed in its open activatable form in the endoplasmic reticulum (ER) and consequently must be protected against ER-resident PDI activity. Here, we show that the chaperone 78-kDa glucose-regulated protein (GRP78) protects the MPD against PDI-dependent disulfide-bond isomerization by binding to this domain and, thereby, preventing ADAM17 inhibition.

MATERIALS
Product Number
Brand
Product Description

Supelco
Malachite Green chloride, analytical standard
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
VER-155008, ≥98% (HPLC)
SKU
Pack Size
Availability
Price
Quantity