Structure/function studies on vascular cell adhesion molecule-1.
Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig) superfamily which interacts with the integrin very late antigen-4 (VLA4). The VCAM1/VLA4 interaction mediates both adhesion and signal transduction and is thought to play an important role in inflammatory and immune responses in vivo. The major form of human VCAM1 contains seven extracellular Ig-like domains, with domain 1 designated as the most N-terminal. We have examined the relationship between human VCAM1 structure and function using a combination of domain truncation mutants and proteolytic fragmentation of recombinant soluble VCAM1. We have characterized two regions of VCAM1, localized to domains 4 and 5, which are highly sensitive to proteolytic cleavage, localized the epitope of the blocking monoclonal antibody 4B9 to domain 1, and found that domains 1-3 are sufficient for both its adhesive function and its ability to initiate T cell activation.
Pepinsky
B
B
Biogen, Inc., Cambridge, Massachusetts 02142.
Hession
C
C
Chen
L L
LL
Moy
P
P
Burkly
L
L
Jakubowski
A
A
Chow
E P
EP
Benjamin
C
C
Chi-Rosso
G
G
Luhowskyj
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000302:isolation & purification; D016029:Receptors, Very Late Antigen / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1