Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding.
Metalloprotease-disintegrins (ADAMs) have captured our attention as key players in fertilization and in the processing of the ectodomains of proteins such as tumor necrosis factor (&agr;) (TNF(&agr;)), and because of their roles in Notch-mediated signaling, neurogenesis and muscle fusion. ADAMs are integral membrane glycoproteins that contain a disintegrin domain, which is related to snake-venom integrin ligands, and a metalloprotease domain (which can contain or lack a catalytic site). Here, we review and critically discuss current topics in the ADAMs field, including the central role of fertilin in fertilization, the role of the TNF(&agr;) convertase in protein ectodomain processing, the role of Kuzbanian in Notch signaling, and links between ADAMs and processing of the amyloid-precursor protein.
Schlöndorff
J
J
Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, Box 368, Tri-Institutional (Cornell/ Rockefeller University/Sloan-Kettering Institute) MD/PhD Program, New York, NY 10021, USA.
Blobel
C P
CP
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D005306:Fertilization / Q000502:physiology; D008666:Metalloendopeptidases / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*
D008666:Metalloendopeptidases