An essential role for ectodomain shedding in mammalian development.
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.
Peschon
J J
JJ
Immunex Corporation, Seattle, WA 98101, USA. peschon@immunex.com
Slack
J L
JL
Reddy
P
P
Stocking
K L
KL
Sunnarborg
S W
SW
Lee
D C
DC
Russell
W E
WE
Castner
B J
BJ
Johnson
R S
RS
Fitzner
J N
JN
Boyce
R W
RW
Nelson
N
N
Kozlosky
C J
CJ
Wolfson
M F
MF
Rauch
C T
CT
Cerretti
D P
DP
Paxton
R J
RJ
March
C J
CJ
Black
R A
RA
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*
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