Trends in Genetics
ReviewThe ADAM gene family: surface proteins with adhesion and protease activity
Section snippets
Some ADAM proteases are sheddases
During development and in the adult, cells have the ability to modify their surface to regulate various kinds of functions. For example, the extracellular domain of >40 plasma membrane-anchored cytokines, growth factors, receptors, adhesion molecules and enzymes can be cleaved and thereby released (shed) from the plasma membrane by various proteases (called sheddases or secretases)18. These sheddases are themselves transmembrane proteins and, in several cases, are ADAMs.
One of the best-studied
ADAMTS
In 1999, several reports made it clear that the ADAM proteins with a thrombospondin motif (ADAMTS) represent an important class of proteases that are closely related to ADAMs (31, 32, 33, 34). The ADAMTS proteins for which biological functions have been characterized include gon-1 (involved in gonad formation), ADAMTS-4 (aggrecanase-1) and, the most recently described, ADAMTS-11 (aggrecanase-2). Metalloprotease activity of the gon-1 protein is required for achieving correct organ shape during
Adhesion role of ADAMs in fertilization
Among the 29 ADAMs, there is no basis for predicting how many will be active in cell adhesion because the required active-site residues in the disintegrin domain have not been defined as yet. The best studied ADAM that has adhesion activity is the sperm surface protein, fertilin, which is a heterodimer that contains two subunits, ADAM 1 and 2, also known as fertilin α and β (Fig. 3).
Interest in fertilin arose originally from the finding that an anti-fertilin β monoclonal antibody (mAb) blocks
Conclusions
In the last decade, we have gained many important insights into the ADAM protein family, yet it is easy to feel that there are many questions still to address. Even well-studied ADAMs are surrounded by unanswered questions that concern their regulation, signaling ability and function of each domain. As these many unknowns are analyzed, the area should remain active, dynamic and of broad biological significance.
Acknowledgements
This research was supported by NICHD grants U54-HD29125 and HD 16580.
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2019, Cancer LettersCitation Excerpt :It is known that ADAM-mediated cleavage is essential for G-protein-coupled [20,21] or stress-induced [22] EGF receptor transactivation, and it is modulated by intracellular signaling in response to growth factors, phorbol esters, and changes in tyrosine kinase activity [8]. Interestingly, while ADAM family members harbor cytoplasmic protein-docking motifs [8], cytoplasmically-truncated ADAM10 and ADAM17 are fully functional [23], suggesting only a minor role for the cytoplasmic domains in controlling downstream signaling. ADAM17 is suggested to be regulated by cysteine oxidation that modulates the conformation of its extracellular domain [24,25].