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

Abstract

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.

Purification of ADAM 10 from bovine spleen as a TNFα convertase

“…Fig. 2 shows the protein sequences of these bands are consistent with a known protein ADAM 10 [10], a metalloprotease with an ill-defined biological activity [11,12] (the lower band is a proteolyzed product starting at residue 285). ADAM 10 could cleave 125I-proTNFa to a 17 kDa protein (Fig.…”

“…A homologous protein was recently purified from human Monomac 6 cells (data not shown). The protein was identified as ADAM 10 [10], a protein first purified from bovine brain based on its ability to cleave MBP [11,12]. The protein has since been found in many tissues, and is homologous to the Drosophila kuz protein, suggesting a role in neurogenesis [13].…”

Cell fusion promotes chemoresistance in metastatic colon carcinoma

“…[15][16][17] ADAMs were initially discovered as proteins involved in fertilization, muscle fusion and organ development. 18,19 In this study, we provide evidence that proteins ADAM10, GTP-binding protein a13, radixin, myosin regulatory light chain and RhoA promote cell fusion in colon cancer cells. In addition, we demonstrate that cell fusion results in the acquisition of a resistant phenotype to both 5-FU and Oxa, two pharmacological agents commonly employed in the treatment of advanced colon cancer.…”

TNF-α-Converting Enzyme Cleaves the Macrophage Colony-Stimulating Factor Receptor in Macrophages Undergoing Activation

“…One of the best-characterized members of the ADAM family is TACE (ADAM-17), responsible for the ectodomain shedding of receptors for TNF and other cytokines (11,21). Using anti-TACE, which recognizes the extracellular, catalytic domain of TACE, we found that this enzyme is expressed in BAC macrophages and that its expression is inhibited by the pretreatment of cells with dec-RVKR-cmk (Fig.…”