Dynamic regulation of integrins.
Dynamic regulation of receptor function is a distinguishing feature of the integrin family of adhesion molecules and makes a significant contribution to alterations in cellular adhesive properties. The best characterized example is that of the platelet receptor alpha IIb beta 3 (glycoprotein IIb-IIIa), which does not bind soluble fibrinogen on resting platelets. Following platelet activation, the alpha IIb beta 3 binds soluble fibrinogen with moderately high affinity and platelet aggregation ensues. Similar regulation of receptor function has also been directly demonstrated for alpha 5 beta 1 and alpha M beta 2, and it is likely that it is a general property of all members of the family. The altered ligand binding affinity is due to a change in the conformation of the external domain of the receptor, in response to intracellular signals that are transmitted the length of the molecule. The cytoplasmic tails of the integrins are active participants in this regulation, and they also mediate interactions with the cytoskeleton. A number of anti-integrin monoclonal antibodies have been described which induce high affinity ligand binding, and certain of these preferentially bind to the high affinity conformation of the receptor. The alteration in conformation allows better access for macromolecular ligands to the ligand binding pocket, which has been mapped (in alpha IIb beta 3) to the amino terminal globular head of the receptor. The precise mechanism by which the activating signal is transferred from within the cell to the distal external domain remains the subject of active research.
Faull
R J
RJ
Department of Renal Medicine, St. George Hospital, Kogarah, NSW, Australia.
Ginsberg
M H
MH
D000818:Animals; D002448:Cell Adhesion; D006801:Humans; D016023:Integrins / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D017469:Receptors, Fibronectin / Q000502:physiology; D015398:Signal Transduction
D016023:Integrins; D016177:Macrophage-1 Antigen; D010980:Platelet Membrane Glycoproteins; D017469:Receptors, Fibronectin