title: The membrane-proximal domain of A Disintegrin and Metalloprotease 17 (ADAM17) is responsible for recognition of the interleukin-6 receptor and interleukin-1 receptor II.
abstract: A great number of physiological processes are regulated by the release of ectodomains of membrane proteins. A Disintegrin And Metalloprotease 17 (ADAM17) is one of the important enzymes, which mediate this process called shedding. Today, more than 70 substrates of this transmembrane metalloprotease are known. This broad spectrum raises the question how ADAM17 recognizes its substrates specifically. Differently tagged ADAM17 deletion variants were used to demonstrate that exclusively the extracellular domains of ADAM17 are needed for interaction with two of its substrates, the IL-6R and the IL-1RII; whereas the transmembrane- and cytoplasmic-region are dispensable for this process. In the extracellular part solely the membrane-proximal domain of ADAM17 is mandatory for recognition of the two type-I transmembrane proteins, but not for the interaction with the type-II transmembrane molecule TNF-α.
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Inken
authors.initials: I
authors.lastname: Lorenzen
authors.forename: Juliane
authors.initials: J
authors.lastname: Lokau
authors.forename: Stefan
authors.initials: S
authors.lastname: Düsterhöft
authors.forename: Ahmad
authors.initials: A
authors.lastname: Trad
authors.forename: Christoph
authors.initials: C
authors.lastname: Garbers
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scheller
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D053574:Receptors, Interleukin-1 Type II / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D053574:Receptors, Interleukin-1 Type II; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse