Monoclonal antibodies as probes of integrin priming and activation.
Integrins are a family of heterodimeric, transmembrane receptors that mediate a range of cell-cell and cell-extracellular matrix interactions in an array of physiological and pathophysiological situations. Integrin-mediated cell adhesion is dynamically regulated in vivo to facilitate cell anchorage and movement, but prevents aberrant trafficking and aggregation. Following ligand engagement, integrin signalling imposes a spatial constraint on the assembly of signalling complexes and controls the transduction of mechanical force to the cytoskeleton. This transmembrane passage of signals via integrins is achieved both by clustering of receptors, which makes the ligand and effector engagement more favourable kinetically, and by induction of conformational changes, that theoretically creates ligand and effector binding sites de novo. Clustering and conformational changes can be triggered both from the inside of the cell (resulting in acquisition of ligand-competent conformers) and from the outside (ligand-induced signalling). In this paper, these processes will be described and distinguished by the terms priming and activation, respectively. Although both clustering and conformation are important for integrin function, the latter will be the main focus of this article; in particular, the importance of monoclonal antibodies for the study of integrin shape changes.
Humphries
M J
MJ
Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK. martin.humphries@man.ac.uk
D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001665:Binding Sites; D002448:Cell Adhesion; D002450:Cell Communication; D018360:Crystallography, X-Ray; D003599:Cytoskeleton / Q000378:metabolism; D004252:DNA Mutational Analysis; D019281:Dimerization; D000939:Epitopes; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry; D016023:Integrins / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000939:Epitopes; D039081:Integrin alpha5beta1; D016023:Integrins; D008024:Ligands