title: An essential role for ectodomain shedding in mammalian development.
abstract: The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.
authors.affiliation: Immunex Corporation, Seattle, WA 98101, USA. peschon@immunex.com
authors.forename: J J
authors.initials: JJ
authors.lastname: Peschon
authors.forename: J L
authors.initials: JL
authors.lastname: Slack
authors.forename: P
authors.initials: P
authors.lastname: Reddy
authors.forename: K L
authors.initials: KL
authors.lastname: Stocking
authors.forename: S W
authors.initials: SW
authors.lastname: Sunnarborg
authors.forename: D C
authors.initials: DC
authors.lastname: Lee
authors.forename: W E
authors.initials: WE
authors.lastname: Russell
authors.forename: B J
authors.initials: BJ
authors.lastname: Castner
authors.forename: R S
authors.initials: RS
authors.lastname: Johnson
authors.forename: J N
authors.initials: JN
authors.lastname: Fitzner
authors.forename: R W
authors.initials: RW
authors.lastname: Boyce
authors.forename: N
authors.initials: N
authors.lastname: Nelson
authors.forename: C J
authors.initials: CJ
authors.lastname: Kozlosky
authors.forename: M F
authors.initials: MF
authors.lastname: Wolfson
authors.forename: C T
authors.initials: CT
authors.lastname: Rauch
authors.forename: D P
authors.initials: DP
authors.lastname: Cerretti
authors.forename: R J
authors.initials: RJ
authors.lastname: Paxton
authors.forename: C J
authors.initials: CJ
authors.lastname: March
authors.forename: R A
authors.initials: RA
authors.lastname: Black
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development; D019041:L-Selectin / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse