A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis.
TWEAK is a member of the TNF ligand family that induces angiogenesis in vivo. We report cloning of a receptor for TWEAK (TweakR) from a human umbilical vein endothelial cell (HUVEC) library. The mature form of TweakR has only one hundred and two amino acids and six cysteine residues in its extracellular region. Five different assays demonstrate TWEAK-TweakR binding, and the interaction affinity constant (Kd) is within a physiologically relevant range of 2.3 +/- 0.1 nM. The TweakR cytoplasmic domain binds TRAFs 1, 2, and 3. Cross-linking of TweakR induces HUVEC growth, and mRNA levels are upregulated in vitro by a variety of agents and in vivo following arterial injury. Soluble TweakR inhibits endothelial cell migration in vitro and corneal angiogenesis in vivo.
Wiley
S R
SR
Immunex Corporation, 51 University Street, Seattle, WA 98101, USA. wileys@immunex.com
Cassiano
L
L
Lofton
T
T
Davis-Smith
T
T
Winkles
J A
JA
Lindner
V
V
Liu
H
H
Daniel
T O
TO
Smith
C A
CA
Fanslow
W C
WC
D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000074049:Cytokine TWEAK; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D016415:Sequence Alignment; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D000074049:Cytokine TWEAK; D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors