Alternative splicing of human VCAM-1 in activated vascular endothelium.
Vascular cell adhesion molecule 1 (VCAM-1)/inducible cell adhesion molecule 110 is a mononuclear leukocyte-selective adhesion molecule, expressed on vascular endothelium following activation by certain cytokines or endotoxin. This inducible transmembrane protein and member of the immunoglobulin gene superfamily was previously reported to contain six immunoglobulinlike domains. Using the polymerase chain reaction, a VCAM-1 cDNA was obtained from mRNA of interleukin-1 (IL-1)-treated cultured human umbilical vein endothelial cells (HUVEC). The cDNA clone contained an additional 276 base-pair (bp) domain, located between domains 3 and 4. This new domain is most homologous to the existing N-terminal domain (domain 1). The internal 276-bp region is encoded by a single exon of the human VCAM-1 gene, indicating that the two forms of mRNA arise by alternative splicing. Both forms of VCAM-1 mRNA were detected by polymerase chain reaction in IL-1-stimulated HUVEC, although the seven-domain form appeared predominant. On the surface of HUVEC only a 110-kd polypeptide, consistent with the seven-immunoglobulinlike domain form of VCAM-1, was detectable by immunoprecipitation. Alternative splicing of the VCAM-1 gene in cytokine-activated endothelium may generate functionally distinct cell-surface adhesion molecules.
Cybulsky
M I
MI
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
Fries
J W
JW
Williams
A J
AJ
Sultan
P
P
Davis
V M
VM
Gimbrone
M A
MA
Collins
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D014471:Umbilical Veins / Q000378:metabolism / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D019010:Vascular Cell Adhesion Molecule-1; D004247:DNA