title: Urokinase-type plasminogen activator receptor induces conformational changes in the integrin alphaMbeta2 headpiece and reorientation of its transmembrane domains.
abstract: The glycosylphosphatidylinositol-linked urokinase-type plasminogen activator receptor (uPAR) interacts with the heterodimer cell adhesion molecules integrins to modulate cell adhesion and migration. Devoid of a cytoplasmic domain, uPAR triggers intracellular signaling via its associated molecules that contain cytoplasmic domains. Interestingly, uPAR changes the ectodomain conformation of one of its partner molecules, integrin alpha(5)beta(1), and elicits cytoplasmic signaling. The separation or reorientation of integrin transmembrane domains and cytoplasmic tails are required for integrin outside-in signaling. However, there is a lack of direct evidence showing these conformational changes of an integrin that interacts with uPAR. In this investigation we used reporter monoclonal antibodies and fluorescence resonance energy transfer analyses to show conformational changes in the alpha(M)beta(2) headpiece and reorientation of its transmembrane domains when alpha(M)beta(2) interacts with uPAR.
authors.affiliation: Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Tang
authors.affiliation: Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
authors.forename: Ardcharaporn
authors.initials: A
authors.lastname: Vararattanavech
authors.affiliation: Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore. Electronic address: smtan@ntu.edu.sg.
authors.forename: Suet-Mien
authors.initials: SM
authors.lastname: Tan
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D017261:Glycosylphosphatidylinositols / Q000737:chemistry; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D016023:Integrins / Q000737:chemistry / Q000378:metabolism; D020014:K562 Cells; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008968:Molecular Conformation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D017261:Glycosylphosphatidylinositols; D039081:Integrin alpha5beta1; D016023:Integrins; D016177:Macrophage-1 Antigen; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator