Cytokine induction of an alternatively spliced murine vascular cell adhesion molecule (VCAM) mRNA encoding a glycosylphosphatidylinositol-anchored VCAM protein.
VCAM-1 is an immunoglobulin superfamily member that mediates adhesion of a variety of leukocytes to endothelial cells. VCAM expression has been associated with a variety of disease states and has been implicated in a number of normal processes. The predominant form of VCAM produced in human endothelial cells is a transmembrane protein containing seven immunoglobulin domains. In this study the murine VCAM gene has been characterized to allow the function(s) of VCAM to be studied in a small genetically accessible animal. While expression of an mRNA encoding a seven-immunoglobulin-domain transmembrane VCAM protein was seen in most tissues, the predominant change in VCAM expression upon interleukin 1 beta treatment was the induction of an alternatively spliced VCAM mRNA containing only the first three immunoglobulin domains. This message encodes a glycosylphosphatidylinositol (GPI)-anchored form of VCAM, VCAMGPI. VCAMGPI was efficiently cleaved from the cell surface by phosphatidylinositol-specific phospholipase C, mediated adhesion to leukocytes in a very late antigen 4-dependent manner, and was produced by mouse endothelial cell lines in culture. These data demonstrate that alternate forms of VCAM are produced under different physiological conditions and suggest that VCAMGPI may have a distinct role in inflammatory processes.
Terry
R W
RW
Molecular Sciences Group, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199.
Kwee
L
L
Levine
J F
JF
Labow
M A
MA
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000302:isolation & purification; D015870:Gene Expression; D017261:Glycosylphosphatidylinositols / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D017261:Glycosylphosphatidylinositols; D007375:Interleukin-1; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D004247:DNA