Catalytic Properties of ADAM19*

By V. Chesneau, J. Becherer, Yufang Zheng, H. Erdjument‐Bromage, Paul Tempst, C. P. Blobel. 2003

128 citations recorded by the source corpus.

ADAMs are membrane-anchored glycoproteins with functions in fertilization, heart development, neurogenesis, and protein ectodomain shedding. Here we report an evaluation of the catalytic activity of recombinantly expressed soluble forms of ADAM19, a protein that is essential for cardiovascular morphogenesis. Proteolytic activity of soluble forms of ADAM19 was first demonstrated by their autocatalytic removal of a purification tag (Myc-His) and their ability to cleave myelin basic protein and the insulin B chain. The metalloprotease activity of ADAM19 is sensitive to the hydroxamic acid-type metalloprotease inhibitor BB94 (batimastat) but not to tissue inhibitors of metalloproteases (TIMPs) 1–3. Moreover, ADAM19 cleaves peptides corresponding to the known cleavage sites of tumor necrosis factor-α (TNF–α), TNF-related activation-induced cytokine (TRANCE, also referred to as osteoprotegerin ligand), and kit ligand-1 (KL-1) in vitro. Although ADAM19 is not required for shedding of TNFα and TRANCE in mouse embryonic fibroblasts, its overexpression in COS-7 cells results in strongly increased TRANCE shedding. This suggests a potential role for ADAM19 in shedding TRANCE in cells where both molecules are highly expressed, such as in osteoblasts. Interestingly, our results also indicate that ADAM19 can function as a negative regulator of KL-1 shedding in both COS-7 cells and mouse embryonic fibroblasts, instead of acting directly on KL-1. The identification of potential in vitro substrates offers the basis for further functional studies of ADAM19 in cells and in mice.

Subfields: Molecular Biology, Oncology

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Citations in the corpus

A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “Also, heparan sulfate glycosaminoglycans (GAGs) enhance TIMP-3 activity and therefore modulate its inhibitory effect on ADAMTS [59].”
Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands (2004, methodology): “In addition, the use of an AP tag has been independently validated using the TNF family members TNF and TRANCE/ OPGL (Zheng et al., 2002; Chesneau et al., 2003).”
ADAMs family and relatives in cardiovascular physiology and pathology. (2016, background): “The catalytic domain of ADAM10 can be inhibited by TIMP1 and TIMP3 in vitro [45], whereas ADAMs 8, 9 and 19 do not exhibit susceptibility to TIMP-mediated inhibition [46,47].”
Essential Role for ADAM19 in Cardiovascular Morphogenesis (2004, background): “Furthermore, overexpression of ADAM19 increases ectodomain release of tumor necrosis factor-related activation-induced cytokine (TRANCE, also referred to as osteoprotegerin-ligand [OPGL]) (7), a protein with important roles in osteoclast differentiation, dendritic cell survival, and mammary gland de”
Essential roles of Meltrin β (ADAM19) in heart development (2004, background): “Furthermore, TNF-related activation-induced cytokine (TRANCE) was reported to be another candidate substrate (Chesneau et al., 2003).”
The ADAM metalloproteinases (2008, background): “The catalytic domain of ADAM-10 is inhibited by both TIMP-1 and TIMP-3 (Amour et al., 2000) , whereas ADAM-8, -9 and -19 defy any pattern and are insensitive to TIMP inhibition (Amour et al., 2002; Chesneau et al., 2003) .”