The ADAMs family of metalloproteases: multidomain proteins with multiple functions

  1. Darren F. Seals and
  2. Sara A. Courtneidge1
  1. Van Andel Research Institute, Grand Rapids, Michigan 49503, USA

This extract was created in the absence of an abstract.

The ADAMs family of transmembrane proteins belongs to the zinc protease superfamily. Members of the family have a modular design, characterized by the presence of metalloprotease and integrin receptor-binding activities, and a cytoplasmic domain that in many family members specifies binding sites for various signal transducing proteins. The ADAMs family has been implicated in the control of membrane fusion, cytokine and growth factor shedding, and cell migration, as well as processes such as muscle development, fertilization, and cell fate determination. Pathologies such as inflammation and cancer also involve ADAMs family members. Excellent reviews covering various facets of the ADAMs literature-base have been published over the years and we recommend their examination (Black and White 1998; Schlondorff and Blobel 1999; Primakoff and Myles 2000;Evans 2001; Kheradmand and Werb 2002). In this review, we will first discuss the properties of each of the domains of the ADAMs. We will then go on to describe the involvement of ADAMs in selected biological processes. Then, we will highlight recent interesting findings suggesting roles for ADAMs in human disease. Finally, we look to the future and discuss some of the open issues in ADAMs function and regulation.

ADAMs are members of the zinc protease superfamily

Zinc proteases are subdivided according to the primary structure of their catalytic sites and include gluzincin, metzincin, inuzincin, carboxypeptidase, and DD carboxypeptidase subgroups (Hooper 1994). The metzincin subgroup (to which the ADAMs belong) is further divided into serralysins, astacins, matrixins, and adamalysins (Stocker et al. 1995). The matrixins comprise the matrix metalloproteases, or MMPs. These enzymes are the principle agents responsible for extracellular matrix degradation and remodeling, and play important roles in development, wound healing, and in the pathology of diseases such as arthritis and cancer (Chang and Werb 2001). Adamalysins are similar to the matrixins in their metalloprotease domains, but contain a …

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