ADAM, a novel family of membrane proteins containing A Disintegrin And Metalloprotease domain: multipotential functions in cell-cell and cell- matrix interactions

C ELL--cell and cell-matrix adhesion, as well as proteolysis of the extracellular matrix, are vital for normal processes such as tissue morphogenesis and wound healing, as well as for pathologies such as tumor cell invasion and metastasis. A variety of cell surface adhesion proteins and proteases are important players in these events. Families of membrane-anchored cell surface adhesion molecules include cadherins, immunoglobulin superfamily members, selectins, integrins, and syndecans (7). Membrane-anchored cell surface proteases include membrane-type matrix metalloprotease (4) and meprin (9). In this review we describe the ADAMs, a recently discovered gene family encoding membrane proteins with A Disintegrin And Metalloprotease domain. ADAMs 1 are unique among cell surface proteins in possessing both a potential adhesion domain as well as a potential protease domain. ADAM cDNAs have been found in a wide array of mammalian tissues as well as in lower eukaryotes (Tables I and II). The eleven full-length members described to date encode proteins of 750-800 amino acids which contain pro-, metalloprotease-like, disintegrin-like, cysteinerich, EGF-like, transmembrane, and cytoplasmic domains (Table I, legend). Although these domains are not similar in sequence to those of other membrane-anchored adhesion molecules or proteases, they are related to domains found in a family of soluble snake venom proteins, the snake venom metalloproteases (SVMPs) (5). SVMPs are encoded by three cDNA classes. N-I encodes pro and metalloprotease domains, N-II encodes pro, metalloprotease, and disintegrin domains, and N-III encodes pro, metalloprotease, disintegrin-like, and cysteine-rich domains. We will refer to the primary translation products as P-I, P-II, and P-III, respectively. In a snake bite victim, snake venom metalloproteases and disintegrins promote hemorrhage. Soluble metalloproteases degrade capillary basement