Activation of ADAM 12 protease by copper

F Loechel; Ulla M. Wewer

Activation of ADAM 12 protease by copper

F Loechel, Ulla M. Wewer

14 Citations (Scopus)

Abstract

Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency: elimination of the ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on copper activation, whereas mutation of an unpaired cysteine residue in the catalytic domain resulted in a mutant form of ADAM 12-S that was insensitive to copper. This suggests a multi-step activation mechanism for ADAM 12 involving both furin cleavage and copper binding.

Original language	English
Journal	FEBS Letters
Volume	506
Issue number	1
Pages (from-to)	65-68
Number of pages	4
ISSN	0014-5793
Publication status	Published - 2001

Keywords

ADAM Proteins
Alpha-Globulins
Blotting, Western
Chromatography, Gel
Copper
Enzyme Activation
Humans
Membrane Proteins
Metalloendopeptidases
Recombinant Proteins

Cite this

@article{4907e65074c711dbbee902004c4f4f50,

title = "Activation of ADAM 12 protease by copper",

abstract = "Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency: elimination of the ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on copper activation, whereas mutation of an unpaired cysteine residue in the catalytic domain resulted in a mutant form of ADAM 12-S that was insensitive to copper. This suggests a multi-step activation mechanism for ADAM 12 involving both furin cleavage and copper binding.",

keywords = "ADAM Proteins, Alpha-Globulins, Blotting, Western, Chromatography, Gel, Copper, Enzyme Activation, Humans, Membrane Proteins, Metalloendopeptidases, Recombinant Proteins",

author = "F Loechel and Wewer, {Ulla M.}",

year = "2001",

language = "English",

volume = "506",

pages = "65--68",

journal = "F E B S Letters",

issn = "0014-5793",

publisher = "JohnWiley & Sons Ltd",

number = "1",

}

TY - JOUR

T1 - Activation of ADAM 12 protease by copper

AU - Loechel, F

AU - Wewer, Ulla M.

PY - 2001

Y1 - 2001

N2 - Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency: elimination of the ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on copper activation, whereas mutation of an unpaired cysteine residue in the catalytic domain resulted in a mutant form of ADAM 12-S that was insensitive to copper. This suggests a multi-step activation mechanism for ADAM 12 involving both furin cleavage and copper binding.

AB - Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency: elimination of the ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on copper activation, whereas mutation of an unpaired cysteine residue in the catalytic domain resulted in a mutant form of ADAM 12-S that was insensitive to copper. This suggests a multi-step activation mechanism for ADAM 12 involving both furin cleavage and copper binding.

KW - ADAM Proteins

KW - Alpha-Globulins

KW - Blotting, Western

KW - Chromatography, Gel

KW - Copper

KW - Enzyme Activation

KW - Humans

KW - Membrane Proteins

KW - Metalloendopeptidases

KW - Recombinant Proteins

M3 - Journal article

C2 - 11591372

SN - 0014-5793

VL - 506

SP - 65

EP - 68

JO - F E B S Letters

JF - F E B S Letters

IS - 1

ER -

Activation of ADAM 12 protease by copper

Abstract

Keywords

Fingerprint

Cite this