Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule.
Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein whose cell surface expression is induced under inflammatory conditions. It has been shown previously to participate in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. We report here that the VAP-1 cDNA encodes a type II transmembrane protein of 84.6 kD with a single transmembrane domain located at the NH2-terminal end of the molecule and six potential N-glycosylation sites in the extracellular domain. In vivo, the protein exists predominantly as a homodimer of 170-180 kD. Ax endothelial cells transfected with a VAP-1 cDNA express VAP-1 on their cell surface and bind lymphocytes, and the binding can be partially inhibited with anti-VAP-1 mAbs. VAP-1 has no similarity to any currently known adhesion molecules, but has significant identity to the copper-containing amine oxidase family and has a monoamine oxidase activity. We propose that VAP-1 is a novel type of adhesion molecule with dual function. With the appropriate glycosylation and in the correct inflammatory setting, its expression on the lumenal endothelial cell surface allows it to mediate lymphocyte adhesion and to function as an adhesion receptor involved in lymphocyte recirculation. Its primary function in other locations where it is expressed, such as smooth muscle, may depend on its inherent monoamine oxidase activity.
Smith
D J
DJ
MediCity Research Laboratories, University of Turku, FIN-20520 Turku, Finland. david.smith@biote.fi
Salmi
M
M
Bono
P
P
Hellman
J
J
Leu
T
T
Jalkanen
S
S
D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry* / Q000502:physiology; D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D004730:Endothelium, Vascular / Q000502:physiology; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000378:metabolism; D009439:Neuraminidase; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012795:Sialoglycoproteins / Q000737:chemistry; D013379:Substrate Specificity
D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D009439:Neuraminidase