Down-regulation of integrin alpha M beta 2 ligand-binding function by the urokinase-type plasminogen activator receptor.
The cell adhesion molecule integrin alphaMbeta2 associates with the urokinase-type plasminogen activator receptor (uPAR) on monocytes and neutrophils. uPAR also associates with members of the beta1 and beta3 integrins, and it modulates the ligand-binding function of these integrins. In this study, we showed that co-expressing uPAR with alphaMbeta2 in 293 transfectants down-regulated the ligand-binding capacity of alphaMbeta2 to denatured protein, fibrinogen, and intercellular adhesion molecule 1 (ICAM-1). Migration of transfectants on fibrinogen mediated by alphaMbeta2 was reduced in the presence of uPAR. In addition, the constitutive ligand-binding property of an alphaMbeta2 mutant was attenuated by its association with uPAR. Co-immunoprecipitation analyses using a panel of alphaMbeta2-specific mAbs suggest shielding of the ligand-recognition site of alphaMbeta2 by uPAR.
Tang
Man-Li
ML
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Kong
Le-Sheng
LS
Law
S K Alex
SK
Tan
Suet-Mien
SM
D000911:Antibodies, Monoclonal / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D008024:Ligands; D016177:Macrophage-1 Antigen; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator