Urokinase-type plasminogen activator receptor induces conformational changes in the integrin alphaMbeta2 headpiece and reorientation of its transmembrane domains.
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.
Tang
Man-Li
ML
Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
Vararattanavech
Ardcharaporn
A
Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
Tan
Suet-Mien
SM
Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore. Electronic address: smtan@ntu.edu.sg.
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
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