The metalloprotease ADAM8 is associated with and regulates the function of the adhesion receptor PSGL-1 through ERM proteins.
The P-selectin glycoprotein ligand-1 (PSGL-1) is involved in the initial contact of leukocytes with activated endothelium, and its adhesive function is regulated through its proteolytic processing. We have found that the metalloprotease ADAM8 is both associated with PSGL-1 through the ezrin–radixin–moesin actin-binding proteins and able to cause the proteolytic cleavage of this adhesion receptor. Accordingly, ADAM8 knockdown increases PSGL-1 expression, and functional assays show that ADAM8 is able to reduce leukocyte rolling on P-selectin and hence on activated endothelial cells. We conclude that ADAM8 modulates the expression and function of PSGL-1.
Servicio de Reumatología, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain.
Maria
M
Domínguez-Luis
Amalia
A
Lamana
Jesús
J
Vazquez
Rósula
R
García-Navas
Faustino
F
Mollinedo
Francisco
F
Sánchez-Madrid
Federico
F
Díaz-González
Ana
A
Urzainqui
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D036904:Leukocyte Rolling / Q000502:physiology; D007962:Leukocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C084882:P-selectin ligand protein; D019038:Platelet Glycoprotein GPIb-IX Complex; D014157:Transcription Factors; C094990:adhesion receptor; D051722:ADAM Proteins; C068490:ADAM8 protein, human