Murine VCAM-1. Molecular cloning, mapping, and analysis of a truncated form.
Vascular cell adhesion molecule-1 (VCAM-1) is a member of the Ig superfamily that shows increased expression in a number of pathologic conditions. The role of VCAM-1 in human disease remains undefined and murine models are being extensively studied to help define the importance of VCAM-1 in inflammatory disorders. We have cloned and characterized the murine Vcam1 gene including 3 kb of 5'-flanking sequences and mapped the gene to chromosome 3 near Amy1. cDNA clones isolated from a stimulated hepatic library were found to encode a truncated form of VCAM-1 (T-VCAM-1) which contains Ig domains 1 through 3 and has a unique alternative carboxyl terminus. This form arises by alternative splicing. High level expression of T-VCAM-1 in transfected L cells was sufficient to support adhesion of lymphocytes, and this adhesion was blocked by Abs to VCAM-1. Treatment of transfected COS cells with phospholipase C led to reduced levels of T-VCAM-1 on the cell surface consistent with glycosylphosphatidylinositol linkage. Northern blot analysis showed that mRNA for T-VCAM-1 is inducible in multiple tissues after stimulation with endotoxin. Both forms of VCAM-1 were expressed in cultured endothelial, fibroblast, and aortic smooth muscle cells, whereas neither form was observed in monocyte- and lymphocyte-derived lines. Differential regulation of both forms of VCAM-1 was observed in the three different cell types that are present in the vessel wall. Thus, expression of VCAM-1 is restricted and controlled at the level of transcription and by alternative splicing.
Kumar
A G
AG
Department of Internal Medicine, Baylor College of Medicine, Houston, TX 77030.
Dai
X Y
XY
Kozak
C A
CA
Mims
M P
MP
Gotto
A M
AM
Ballantyne
C M
CM
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005260:Female; D005434:Flow Cytometry; D007739:L Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010740:Phospholipases / Q000378:metabolism; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015183:Restriction Mapping; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D010740:Phospholipases