The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage.
CD14 is a myeloid differentiation Ag expressed primarily on peripheral blood monocytes and macrophages. Although its function is unknown, the CD14 gene maps to a region encoding several myeloid growth factors and receptors. Analysis of the CD14 protein sequence deduced from the cDNA shows that although the CD14 protein contains a characteristic leader peptide, it lacks a characteristic transmembrane region, suggesting that CD14 may be anchored to the membrane via glycosylphosphatidylinositol (PI). Treatment of monocytes as well as a CD14-expressing neuroglioma cell line with PI-phospholipase C removed CD14 from the cell surface. Furthermore, monocytes from a patient with paroxysmal nocturnal hemoglobinuria, a disease characterized by lack of expression of other PI-linked proteins, failed to express CD14. Interestingly, the CD14-expressing neuroglioma cell line, which had been transfected with a single CD14 cDNA, released a soluble form of CD14 into the supernatant. Soluble forms of CD14 have previously been observed in serum of normal individuals and in culture supernatants of CD14+ cells. Biosynthetic experiments reveal that this soluble form of CD14 (48 kDa), which is smaller than the form released from the membrane by PI-phospholipase C (53 kDa), does not contain ethanolamine, the first constitutent of the PI-anchoring system. These studies demonstrate that CD14 is a member of the family of PI-anchored proteins and suggest that soluble forms of CD14 represent molecules that completely lack the PI-anchoring system.
Haziot
A
A
Cellular and Molecular Biology Unit, Hospital for Joint Diseases, New York 10003.
Chen
S
S
Ferrero
E
E
Low
M G
MG
Silber
R
R
Goyert
S M
SM
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000302:isolation & purification* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D008563:Membrane Lipids / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000276:immunology* / Q000378:metabolism; D011233:Precipitin Tests; D011487:Protein Conformation; D010738:Type C Phospholipases
D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D010738:Type C Phospholipases